NEWSLETTER

Australasian Society for Immunology Incorporated PP 341403100035 ISSN 1442-8725 June 2011

Providing Health Benefi ts Using DNA Vaccines Oscar Haigh Sir Albert Sakzewski Virus Research Centre (SASVRC), Clinical Medical Virology Centre, University of Queensland, and Royal Children’s Hospital, Herston, Brisbane, Australia

Overview from our studies. Immunising people with disease-preventing vaccines is the second most effective In contrast, the inclusion of localisation signals intervention for preserving good health. Most that target immunogens to the proteasome can vaccines currently in use principally rely on generate Th-1-type CTL responses, thus the elicitation of antibody-mediated immune enhancing immunogenicity. Hepatitis B responses to neutralise pathogens before surface antigen (HBsAg) spontaneously self they infect host cells. However, it is unlikely assembles with host lipid after translation, a that such vaccines provide full sterilising process critical for VLP formation. HBsAg immunity, especially against viruses, as it is is highly immunogenic as a VLP vaccine, extremely diffi cult to prevent some virions and when delivered as a DNA vaccine infecting host cells. To prevent disease caused powerful CTL responses are generated. by viruses, such as respiratory syncytial When HBsAg-based DNA vaccines are virus (RSV), human papillomavirus (HPV) cont. p4 and HIV, the generation of antigen-specifi c cytotoxic T-lymphocyte (CTL) responses is Bob Tindle Contents required to kill virus-infected cells. Similarly, Providing health benefi ts using DNA cancer cells which present unique proteins is cheap to produce and purify on a large vaccines 1 that can be targeted by the immune system, scale, and with current genetic engineering Editorial 3 i.e. immunogenic tumours are also likely to techniques highly complex, or simple and History of the ASI 6 require such CTL responses. effective DNA elements can be produced. Upon immunisation, host cells take up the ASI Council, what it is, what it does 15 The principal goal of the Viral Immunology DNA plasmids and the encoded immunogens Quickfi re Immunology Series, QIMR 16 Unit (VIU), headed by Professor Robert are subsequently expressed endogenously. Bursa Fabricius Scandal 17 Tindle, is to devise immunisation strategies These proteins are processed to produce for various viral diseases and cancers, for immunogenic epitopes that are presented Visiting Speaker Program 18 which there is currently no vaccine or practical through the major histocompatibility complex New Investigator Prize 19 therapy available. DNA vaccines elicit class I (MHC-I) pathway or cross presented Obituary: Jurg Tschopp 20 immune responses frequently superior to those on class II molecules. DNA vaccines are Upcoming Conferences 21 induced by conventional vaccines. Clinical highly stable and do not result in inhibitory trials have demonstrated immunogenicity vector-directed immune responses that are a Councillors’ News 22 and powerful immunostimulation by DNA problem using viral vector strategies. DNA Poster Prize Winner 25 vaccines, which refute the dogma that DNA vaccines can be exploited to express virus- International DoI, Melbourne 26 vaccines are weak immunogens and limited like particle (VLP)-forming immunogens, stimulators of immune responses. The use which are amenable to secretion from cells to Queensland DoI 28 of modern DNA vaccine delivery techniques elicit antibody-mediated immune responses, Student News 29 provides simple methods to effectively or responses to exogenous antigen. We Travel Award Conference Reports 30 deliver DNA to the appropriate tissue to have learnt much about the constraints and stimulate immune responses. Plasmid DNA requirements involved in particle formation Publications List 38 ASI Inc. Newsletter June 2011

ASI Inc. COUNCIL Non-Voting Councillors: Newsletter Editor President Past President Dr Simon Apte Dr David Tarlinton Prof Miles Davenport Ph: 61 7 3362 0380 Walter & Eliza Hall Institute of Medical Centre for Vascular Research Email: [email protected] Research University of New South Wales 1G Royal Parade, Parkville Vic 3050 Kensington NSW 2052 Journal Editor Ph: 61 3 9345 2615 Ph: 61 2 9385 2762 Dr Gabrielle Belz Email: tarlinton@wehi.edu.au Email: [email protected] Ph: 61 3 9345 2544 Fax: 61 3 9347 0852 Email: [email protected] Honorary Secretary Honorary Treasurer Dr Susanne Heinzel Dr Pablo Silveira Visiting Speakers Co-ordinator Walter & Eliza Hall Institute of Garvan Institute A/Prof J. Alejandro Lopez Medical Research 384 Victoria Street Queensland Institute of Medical Research 1G Royal Parade, Parkville Vic 3050 Darlinghurst NSW 2010 CBCRC/I, Post Offi ce Ph: 61 3 9345 2609 Ph: 61 2 9295 8429 Royal Brisbane Hospital Qld 4029 Email: [email protected] Email: [email protected] Ph: 61 7 3845 3794 Fax: 61 7 3845 3510 Email: Email: [email protected] State Councillors New South Wales Victoria & Tasmania Council Member of IUIS Dr Stuart Tangye Dr Stuart Berzins Dr Franca Ronchese Ph: 61 2 9295 8455 Ph: 61 3 8344 5706 Ph: 64 4 499 6914 ext 828 Email: [email protected] Email: [email protected] Email: [email protected]

Queensland South Australia & Northern Territory Honorary Archivist & Webmaster: Dr Ashraful Haque Dr Michele Grimbaldeston Dr Judith Greer Ph: 61 7 3362 0414 Ph: 61 8 8222 3083 Ph: 61 7 3346 6018 Email: [email protected] Email: [email protected] Email: [email protected] Western Australia Australian Capital Territory Administrative Correspondence Dr Alec Redwood Dr Stephen Daley Ms Judi Anderson Ph: 61 8 9346 2512 Ph: 61 2 6125 7605 ASI Inc. Secretariat Email: [email protected] Email: [email protected] PO Box 7108 Upper Ferntree Gully Vic 3156 New Zealand Ph: 61 3 9756 0128 Fax: 61 3 9753 6372 Dr Anne LaFlamme Email: [email protected] Ph: 64 4 463 6093 Email: anne.lafl [email protected] ASI Student Representatives FIMSA Councillor Contact for Tasmania Ms Kate Parham Dr Guna Karupiah Dr Greg Woods Ph: 61 8 8222 3727 Ph: 61 2 6125 4562 Tel: 61 3 6226 4830 Email: [email protected] Email: [email protected] Email: [email protected] Ms Wai-Yan (Kiwi) Sun Ph: 61 8 8222 3852 Email: [email protected]

Website The ASI web site (www.immunology.org.au) has been fully remodelled and updated. New services include: ¾ Downloadable forms for ASI awards, ¾ Positions vacant pages, ¾ Jobs wanted pages, ¾ Upcoming conferences listings, as well as a plethora of links to sites of immunological interest at home and abroad. If you‛d like your lab home pages linked to the site, would like to advertise a job or conference, or have a favourite immunology-related site that doesn‛t currently appear on the ASI site, please email Judy Greer at [email protected]

Email bulletin board To subscribe to the ASI bulletin board, send an email to [email protected] with the message: subscribe anz-imm.

2 ASI Inc. Newsletter June 2011

EDITORIAL

It’s been an unusual three months for medical year will be the 50th anniversary of the Special congratulations must go to researchers in Australia. Who would have genesis of ASI and the annual meeting. We high profi le ASI member Professor Ian imagined that the fl eeting euphoria that exists have certainly come a long way, with our Frazer who was recently elected as a after grant submission would be cut short by membership now around one thousand, and Fellow of the Royal Society. This is a the news of a predicted reduction of 20% to our Society continues to support its members great recognition of Ian’s contribution the NHMRC budget? While the rationale and run very successful conferences while to Science and Public Health and we behind the leaking of this information seems maintaining a balance sheet many businesses can all be proud of his achievement and to have been a way of gauging public opinion, would be envious of. This, of course, is due appreciative of his continuing support the magnitude of the public response and to the enormous amount of work put into the for ASI. outrage was surprising indeed. Even more Society behind the scenes by the members surprising was the announcement on Budget and, in particular, the Executive. This year Other features in this edition include night that there would actually be a 4.3% two very important Executive positions will reports on Day of Immunology activities increase in the NHMRC budget (as well as an be coming up for election (Vice President and and Travel Awards, and our continuing increase in the ARC budget). There doesn’t Honorary Secretary) as well as a number of list of publications by ASI members seem to be any doubt that this turnaround was Council positions. Our Secretary (Susanne for the preceding three months. Thank due to the very well organised social media Heinzel) has written an informative article you to everyone who submitted their campaigns and good old fashioned public for this edition that describes the work of the publications in the requested PMID demonstrations. So here we may have the Council which I encourage you to read and to format (which was amazingly 100%!). opportunity to learn an important lesson: if then consider how you may participate. Please encourage any ASI members we are organised and we are vocal, people that you are aware of who have not will listen. I’m sure we knew that already, we It was very sad to learn of the untimely submitted their publications to do so as are trained observers after all, but actually death of Prof. Jürg Tschopp who had a we are hoping that this will become an getting away from the bench or desk and long and close relationship with many important measure of ASI’s collective doing something about it is something novel Australian immunologists. Jürg’s work on impact. Which brings me nicely back for many of us. No doubt the thousands of the infl ammasome and subsequent fi ndings to the start of this editorial; if by our researchers who took to the streets in their and translation of work on IL-1β was an collective action this year we were able labcoats had an impact, but the truly inspiring inspiration to all who became familiar with to encourage the Government to go from demonstrators were the survivors who clearly the work. An obituary by his friends and a 20% reduction to a 4% increase in the and succinctly put forward the case of why colleagues Andreas Strasser and Fabienne NHMRC budget, then next year, is an medical research should be supported and Mackay is printed in this edition. increase of 24% not possible? cherished. Elsewhere in this edition you will fi nd items Simon Apte One such survivor in Brisbane was Danielle highlighting the work of Stacey Walters and Tindle. Danielle, a Hodgkin’s Lymphoma Bernice Tan who won the New Investigator survivor, is the daughter of ASI member Award and Poster Prize, respectively, at last Professor Robert Tindle, and the story of year’s ASI conference in Perth. It has been how Prof. Tindle’s cutting edge research on refreshing to read the concise and interesting stem cells led to the treatment that saved descriptions by Stacey and Bernice, and also Danielle’s life is an inspiration at many levels the articles by the other ASI prize winners that (see Australian Story, http://www.abc.net.au/ were published in the last edition. I encourage austory/content/2005/s1355603.htm). Prof. all students and supervisors to consider Tindle has had an interesting career and our submitting similar lead article this edition by Oscar Haigh details pieces to the some of the work of the last few years within Newsletter; it is the Viral Immunology Unit at the Sir Albert a great way to get Sakzewski Virus Research Centre, both of exposure and you which are headed by Prof. Tindle. could even win $200! We are also very pleased to publish in this issue a comprehensive history of the ASI by Honorary Life Member, Keven J. Turner. Keven has spent a great deal of time and effort carefully recording the events that have shaped our Society and I warmly congratulate him on his efforts. I was very Stacey Walters & surprised to learn from his history that next Bernice Tan

3 ASI Inc. Newsletter June 2011

Providing health benefi ts using DNA been involved in this project, which has immortalisation of the squamous epithelium vaccines, cont. spanned a number of years. This project and neoplastic growth, a result of HPV E6 has focused on eliciting MHC-I-restricted and E7 oncogene expression. E6 and E7 modifi ed to contain ‘foreign’ amino CTL responses to protective epitopes of oncoproteins are essential to maintain a acid sequences from other pathogens a number of diseases simultaneously. transformed cell phenotype and are present in or tumours, appended to HBsAg, the Through exhaustive studies, constraints all stages of cervical intra-epithelial neoplasia powerful immunogenicity of HBsAg on VLP formation were identifi ed by the (CIN), which make them ideal targets for can be harnessed to provide ‘chimeric’ strategy of deleting native HBsAg epitopes immunotherapeutic therapy. Using splice DNA vaccines for a range of different and replacement with foreign epitopes, and overlap extension (SOE)-PCR the HPV-16 diseases. In our lab we have demonstrated this process in some cases did abrogate E6 and E7 oncogenes were fused to HBsAg the effectiveness of this strategy, as we VLP formation. However, the lack of VLPs (E7HBE6), which were mutated to eliminate have demonstrated that fusion to HBsAg did not inhibit CTL responses to encoded oncogenicity. This immunogen delivered as a can enhance CTL responses to multiple epitopes especially when delivered as a DNA vaccine prevented the growth of HPV- antigens. CTL responses to epitopes of DNA vaccine. In fact, a more recent 2009 16-associated TC-1 tumours in all mice. multiple pathogens can be elicited from publication from our lab demonstrated that a single HBsAg-based DNA vaccine appending a polyepitope to HBsAg can When the DNA vaccine was used as a simultaneously. Several approaches can enhance CTL responses to epitopes within therapeutic agent, a signifi cant increase in been employed to generate HBsAg-based the polyepitope. This polyepitope contained survival and decreased tumour volume were fusion immunogens: Individual epitopes, CTL epitopes of a number of different demonstrated. In a TC-1 tumour metastasis or groups of epitopes (‘polyepitope’), may diseases including: HPV, RSV, Infl uenza A model, where mice were inoculated with be inserted within the HBsAg molecule (fl u), human metapneumovirus (hMPV) and TC-1 intravenously, therapy was highly itself, either in the transmembrane or Epstein-Barr virus (EBV)), and pre-existing effective. Mice immunised with HBsAg- luminal regions, or in the external ‘a’- antibody responses in mice did not inhibit HPV DNA vaccines remained 100% tumour determinant. Alternatively, epitopes/ the CTL responses to a number of epitopes free compared to mice immunised with polyepitopes, fragments of proteins, that were tested. CTL responses were elicited HBsAg DNA, of which 80% displayed lung or whole protein, may be appended as to all epitopes simultaneously, even in the tumours. extensions to the N’- or C’- termini, or presence of the powerful SIINFEKL epitope both, of the HBsAg molecule. Protein of ovalbumin. The results of this study have generic expression can be maximized from implications for the design and administration DNA vaccine by using eukaryotic codon This study used A2.1Kb mice, which express of DNA vaccines encoding chimeric optimisation of antigens in design of a transgene encoding alpha-1 and alpha-2 antigens. The specifi c implications from this recombinant HBsAg DNA constructs. domains of HLA-A*0201 fused to the alpha- study include the design of HBsAg-based 3 domain of H-2Kb. The CTL response to DNA vaccines delivering HPV antigens Delivery of foreign antigens by HBsAg- SIINFEKL delayed the growth of B16.OVA for protection against, and as a therapy for, vectored DNA vaccines tumours in mice and murine epitopes afforded HPV-associated squamous carcinomas. An Many diseases and cancer are preventable protection against TC-1 tumour challenge effective therapeutic vaccine designed to treat by eliciting the appropriate immune and inhibited RSV replication in the lungs HPV-associated cancers has the potential to response. A focus of our group’s research of mice after viral challenge. These epitopes dramatically reduce the burden of cervical involves the use of hepatitis B surface could be appended to the termini of HBsAg carcinoma and its associated death rate. antigen (HBsAg) as a vaccine vector as a polyepitope, or inserted into HBsAg to to deliver disease-specific epitopes replace native CTL epitopes. Characterising immunoregulatory or antigens, an idea originating in costimulatory ligands together with conjunction with Dr Hans Netter, now This study has demonstrated that when HBsAg at Monash University. The concept using DNA vaccine delivery, HBsAg is a In 2003 two papers from VIU demonstrated was demonstrated to be effective in powerful vaccine vector which promotes that coexpression of HPV E7 and costimulatory 2006, by Yvonne Woo. In her paper she CTL responses to epitopes of multiple molecules 4-1BB or receptor activator of NF- demonstrated that a CTL response could pathogens simultaneously. kappaB (RANK)/receptor activator of NF- be elicited to either an RSV or HPV kappaB ligand (RANKL), by dendritic cells epitope inserted into HBsAg to replace HBsAg-based vaccines for human (DC) specifi cally, enhanced CTL responses to a native CTL epitope. This vaccine was neoplastic disease E7. Enhanced CTL responses correlated with effective at preventing RSV-associated HBsAg is an attractive vaccine vector for upregulated CD80/86 and MHC-II by DC. lung pathology in a mouse model for delivery of disease-related foreign epitopes. However, coexpression of CD40/CD40L did RSV infection, as well as providing The capacity to elicit CTL responses not enhance CTL responses. When plasmids protection against tumour growth after compares favourably when rHBsAg expressing the costimulatory molecules were tumour challenge with TC-1, a HPV- vaccines are delivered by DNA – rather codelivered with E7-expressing plasmid, as associated murine tumour cell line. These than virus like particle (VLP)-modalities. opposed to coexpression from one plasmid, modifi cations to HBsAg did not abrogate Human papillomavirus (HPV)-associated the adjuvant effects were eliminated. These its secretion from transfected cells. carcinoma is the second most frequent studies have specifi c implications for the cancer causing death in women worldwide. improvement of tumour-antigen-expressing Since then a number of scientists have A major feature of the HPV lifecycle is the DC vaccines.

4 ASI Inc. Newsletter June 2011

A recently initiated follow-on study has vaccine targeting hMPV and RSV at the been exploring novel design approaches same time a possibility. ICB Online Manuscript for the delivery of costimulatory molecules Submission along with foreign viral or cancer antigens, This study has shed light on the role of CTL Online manuscript submission for using HBsAg-VLP as a delivery platform. in the lungs during self-limiting hMPV Immunology and Cell Biology now These molecules include CD70, 4-1BBL, infection and provides a foundation for the available via: RANKL, CD40L and GITRL. Combination development of an hMPV vaccine to elicit http://mc.manuscriptcentral.com/icb of CD70 and HBsAg could almost double CTL responses. This study has resulted in All manuscript submissions to ICB should the number of antigen-specifi c CTL induced the identifi cation of novel human and murine in future be made online via this web site by immunisation. CTL epitopes, the murine CTL epitopes to speed up the reviewing and acceptance of which can provide protection against of manuscripts. These results have the potential to simplify infection in a murine model of infection. Gabrielle Belz, Editor-in-Chief (eliminate the need for boost immunisations) This study suggested that a vaccine eliciting Immunology and Cell Biology and/or enhance (increase effi cacy) of existing CTL responses that target both hMPV and Hepatitis B vaccine. Further research RSV antigens may be viable and could is required to develop to develop next provide great health benefi t in the elderly, generation HBsAg-based vaccines for a range immunocompromised and young children. of human infections and cancer. The work described herein is mostly from Mechanisms of disease caused by human the last few years of which I was privy Sustaining metapneumovirus and protection using a to. Professor Tindle’s scientifi c career has novel polyepitope vaccine been rather comprehensive and originated Membership Human metapneumovirus (hMPV) is a in zoology. Professor Tindle arrived at ASI Inc acknowledges the newly discovered virus and is a signifi cant SASVRC as deputy director in August support of the following respiratory pathogen. hMPV is identifi ed of 1996 from the then-called Centre sustaining member: from respiratory specimens of children for Immunology and Cancer Research suffering from clinical respiratory tract (CICR) as a Lions Kidney and Medical • Jomar Bioscience illness, and may exacerbate wheezing and Research Fellow, where he studied human asthma in young children. There is a body papillomavirus immunobiology with of evidence that suggests that coinfection Professor Ian Frazer. Prof. Tindle formed of hMPV with RSV (a closely related virus) VIU on his arrival at SASVRC and in the can result in more severe long-term sequelae many years before my arrival has published than RSV infection alone. hMPV infection a number of articles in relation to peripheral causes health problems in the elderly and tolerance generated by HPV tumour- An invitation and a request in immunocompromised individuals, but is associated antigen E7, and novel ways of more signifi cant in young children. eliciting CTL-mediated immunity to HPV to all ASI members tumour antigens. Prof. Tindle became the to contribute copy that they think might be interesting, useful, A murine model for natural hMPV infection acting director of SASVRC in 2002 then historical, humorous or thought was developed in the VIU to better understand was appointed Director in 2004. Bob has provoking. cell-mediated immunity elicited by hMPV served SASVRC for 14 years and is now in infection. hMPV-specific interferon-γ- the process of retiring. ¾ We invite our student secreting CD8+ CTL responses were membership to voice their identifi ed in the lungs and airways of mice and During my time at VIU there have been many views on issues that interest results from this study provided a rationale conscientious scientists who contributed or directly concern them. for immuno-intervention, as these responses to the research that I shall acknowledge: may play a role in self-limiting infections. Karen Herd, Dr Yvonne Woo, Dr Michael ¾ It’s our newsletter, so let’s Epitopes were identifi ed and when used as Mather, Huayang Guo, Dr Kristy Edgtton, support it and strive to make it peptide vaccines, these epitopes generated Dr Dekun Chen, Wen Jun Liu, Jason Cheong, even better. effector and memory CTL responses that Dr Melanie Barnes, Dr Scott Thomson and The ASI newsletter comes out were associated with protection against Bob at the helm. I should also acknowledge ¾ 4 times a year and we welcome infection. This study also included the the Sir Albert Sakzewski Virus Research your contributions. identifi cation of hMPV MHC-I-restricted Centre, the home of VIU, which receives CTL epitopes from previously infected core funding from Queensland Health and ¾ AND YOU COULD WIN human patients for use in vaccines. Nine of philanthropic donations from the Sir Albert $200 FOR THE BEST these epitopes were identifi ed from patients Sakzewski Foundation. SASVRC, and ARTICLE PUBLISHED IN with the most common MHC HLA super especially VIU, was a pleasant, productive THE NEWSLETTER! types and are conserved across all strains and friendly atmosphere to work in, and I of hMPV. Interestingly there appears to be enjoyed my time there working with many epitope similarities between these epitopes great scientists including Bob. and those of RSV, making the idea of a

5 ASI Inc. Newsletter June 2011 History of the Australasian Society for Immunology Inc. Keven Turner

Dear Reader,

During a phone conversation I had with Keven Turner some time ago, the topic came up whether the history of ASI from its beginnings to where it is now had ever Former ASI been documented and made available to President, Phil Hodgkin (left) with our members. It soon became clear that, Keven Turner although people had documented certain (Photo: Alan elements or events, a complete history Baxter) did not exist. So the idea of the ‘History of ASI’ was born.

Keven has spent the best part of the past two years collecting information, tracing documents that were almost impossible to fi nd, talking to the people who ‘were there when it happened’, trying to extract as much information as possible about events that in some cases happened nearly 50 years ago. The product of his great Forward These were the momentous decision by efforts and persistence is published in the Sir Macfarlane Burnet in 1957 to change article below. An online version complete In December 1991, to celebrate the 21st the research emphasis of the Walter and with the attachments as referred to in anniversary meeting of the Australian Society Eliza Hall Institute (WEHI) from virology his document is also available from the for Immunology Inc in Perth, the December to immunology and the appointment in ASI website. issue of Immunology and Cell Biology, 1959 of Derrick Rowley to the Chair of Volume 69, contained several articles Microbiology at the Adelaide University. I’d like to take this opportunity to express describing the history of the Society and of The immunological community in Australia our deep thanks to Keven for taking on immunology in Australia. These articles and owes a great debt of gratitude to these two this task, which in many ways seemed to their authors appear below. scientists. turn out to be much more cumbersome than I’m certain he would have ever • The early history of the Australian Macfarlane Burnet’s action provided anticipated at the beginning. Society for Immunology. Derrick the environment for the development of Rowley, pp. 307–308 outstanding immunologists such as Sir Mac I hope you’ll enjoy reading about the • Australian Society for Immunology: the himself, Australia’s fi rst Nobel Laureate in history of the Society! 1970s. Keven Turner, pp. 309–312 immunology, Gus Nossal, Don Metcalf, • Some highs of cellular immunology in Jacques Miller, Alex Szenberg, Noel Warner, Susanne Heinzel the late 1960s, early 1970s: personal Ian Mackay and many others. Through their Hon Secretary refl ection Graham Mitchell, pp. 313– efforts, the WEHI established a reputation 315 as the foremost centre for immunological • Australian Society for Immunology in the research in Australia and one of the most 1980s. Christina Cheers, pp. 317–321 outstanding on the world’s stage – a position • The Australian Society for Immunology it still holds today. in the 1990s and beyond. Geoffrey Shellam, pp. 323–325 With the upgrading of Microbiology in Adelaide University from a section of the This publication builds on and enlarges the Pathology Department to a full department, substance of these excellent articles, covering Derrick Rowley, an immunologist working the period from inception to the conclusion in the Wright–Fleming Institute, London, of 2010. was appointed inaugural Professor. Derrick arrived in Adelaide in January 1960 and Introduction Charles Jenkin followed towards the end Two significant events, which were of that year. At that time they were the only fundamental to the creation of the immunologists in Adelaide but over the Australasian (formerly Australian) Society intervening years, several other Research for Immunology, occurred in the late 1950s. Fellows, post-graduate and graduate students

6 ASI Inc. Newsletter June 2011 joined to make the Department one of the meetings in the 1960s were not lacking in Australian Society for Immunology. premier centres of immunology in the excitement. Particularly memorable were country. the stoushes between the John Curtin School The changes incorporated in 1988 of Medical Research at ANU and the Hall followed the Society becoming an Apart from these two major players, three Institute on the signifi cance of the thymus incorporated body which allowed it to other small groups of immunologists existed for early lymphopoiesis, and the B and T act as a body duly recognized in law, in the early 1960s: one directed by Frank cell dichotomy, including Bede Morris’s giving legal protection to Council and the Fenner at the John Curtin School of Medical famous B…..T wordplay, tactfully referred membership of ASI. It also formalized the Research in Canberra which included Stephen to by Derrick as ‘stimulating and hilarious’ procedure for electing members, giving Boyden and Bede Morris, one directed by and as ‘robust debate’ ”. The thymus has due status to membership of the ASI as Neville Stanley in Perth and the other directed become an obsession with the more vigorous well as defi ning the terms of offi ce of by Bill Halliday in Queensland. young members of the ASI who have made councillors. This extensively modifi ed an award of a thymus (which in reality is constitution was unanimously accepted The Early Years a Bursa of Fabricius), encased in a rather at the AGM held in February 1988. It prominent structure, to the presenter of the provided for a Council comprising the In November 1962, Derrick Rowley invited most hilarious poem at the annual dinners of President, Vice President or Immediate the key immunologists from each of these the scientifi c conferences. Little has changed Past President, Honorary Secretary, four centres to Adelaide for a scientifi c over the past 50 years! Treasurer and representatives of all the meeting which, in reality, was the birth of States and Territories of Australia. It the ASI. The meeting was attended by Sir In December 1969 a symposium on also gave the fl exibility to affi liate with Macfarlane Burnet, Gus Nossal, Gordon Ada ‘Aspects of Antibody Formation and other societies with related interests, and and Alex Szenberg from Melbourne, John Unresponsiveness’ was held in Melbourne created several categories of membership Dineen from Sydney, Stephen Boyden from under the name ‘The Australian Society of such as ordinary, honorary, sustaining, Canberra, Neville Stanley from Perth and Immunologists’. student and associate. There were more Milton Salton, Geoff Cooper, Otto Westphal amendments in 1994, 2009 and 2010. The (visiting Adelaide from Germany), Charles Perth became accepted as an additional latest version of the ASI constitution is Jenkin, Keven Turner, Peter Reeves and PhD venue, with its inaugural meeting being available from the ASI website (www. students from Adelaide. held in December 1970. During this immunology.org.au). meeting Neville Stanley, the Chairman Since the meeting was so successful, the of the Organising Committee, acting on Amalgamation with the New decision was made to hold similar meetings information provided by Gus Nossal, spoke Zealand Society for Immunology annually, with the next meeting to be held about the necessity for the Society to adopt in Melbourne, hosted by the WEHI group. a formal constitution. Seated in the tropical A signifi cant event in the history of David Nelson from Sydney and Ritchie grove adjacent to Winthrop Hall with the song ASI was the amalgamation in 1991 of Nairn from Melbourne joined the foundation of kookaburras and parrots in the background, the Australian Society for Immunology members at this second meeting and, soon those present considered the two compelling with its New Zealand counterpart, the after, the decision was taken that anyone arguments for this: (a) that it was necessary New Zealand Society for Immunology, with an interest in immunology was entitled to fulfi l the requirements for membership to form the Australasian Society for to attend. Informality was the keynote of the in the newly created International Union of Immunology. organization at this stage as it had no formal Immunological Societies (IUIS) and (b) that rules, no constitution and no membership it would assist in the process of obtaining In the mid-1960s, immunology was fees. The only administrative matter that subsidies and reduced airfares for members just beginning to be recognized in New required consideration was the updating of wishing to attend the fi rst International Zealand as a separate research area or a list of those who might be interested in Congress of Immunology to be held in discipline but there were no structural attending future meetings. This informality Washington in August 1971. The motion to meetings in New Zealand to provide a was, however, an unlikely scenario for adopt a constitution, moved by Gus Nossal forum where they could speak to each the future as even by the time of the third and seconded by Gordon Ada, was passed other, except as a group within the meeting convened in Canberra by Kevin unanimously. The Organising Committee for Microbiology Society. Lafferty on 3 and 4 December 1964, the the 1970 meeting in Perth, Neville Stanley, group had been styled the ‘Australian Society Michael Alpers and Keven Turner, was At that time, the Veterinary School was of Immunologists’ (ASI) and a ‘Presidential charged with the responsibility of drafting established in Massey University and Address’ was delivered by Macfarlane the fi rst constitution, which was ratifi ed by there was much enlargement of academic Burnet. the remaining members of the Constitution institutions. In 1968 the School of Committee in time to meet the deadline of Medicine was established in Auckland. In From 1964 to 1969 the venue for these the end of March 1971 for submission to the addition, there were major developments annual meetings rotated between Adelaide, IUIS. This constitution was further ratifi ed by in biological research with the emergence Melbourne, Canberra and Sydney, with the all members attending the annual meeting of of cell biology and molecular biology. It local members accepting full responsibility the Society held in Melbourne in December was the appropriate time to set up in New for all aspects of the organization. Ian 1971, which in reality became the fi rst Zealand an immunology group or society Mackay recalls that “these early informal annual meeting of the properly constituted to the benefi t of all these parties with

7 ASI Inc. Newsletter June 2011

similar or overlapping interests. In May of that year Geoff Shellam, the and professionalism laid the foundation President of ASI, in correspondence with for the administration which exists today. In 1973, John Marbrook and Doug Roger Booth, accepted the problem facing Eventually, however, the task proved too Wilson with the help of Warren Jonas the NZ immunologists and pointed out the much for one person working part time and (Wallaceville, Upper Hutt) and Barbara relative merits of amalgamation re affi liation. the business of the Society was passed to the Heslop (Dunedin) decided to organize These in particular concerned sweeping Victorian Postgraduate Medical Foundation an Immunology meeting in Auckland. changes which he wished to make concerning which acted as Secretariat from 1986 until it This was supported readily by the the expansion of the role of State Branches of downsized in 2000 when the ASI Secretariat Medical Research Council (now HRC) ASI and to ensure that such Branches should was taken over by Judi Anderson Secretarial who provided a grant towards the cost exist in all States and in New Zealand should Services. of the meeting which they termed it become amalgamated. These involved ‘An Interdisciplinary Symposium on assistance in obtaining visiting speakers, The appointment of a secretariat, however, Immunological Topics’. This title was strengthening organizational structures did not remove the need for the annual broad enough to include as many people and in fi nancial assistance together with appointment of offi ce bearers. A list of as possible. The contributions of Ken giving the Branches a stronger role in the offi ce bearers together with the venues of Shortman and Al Cunningham from administration of the ASI. New Zealand the annual scientifi c meetings and, where WEHI and Canberra respectively added would, under amalgamation, enjoy these known, the Conference Chair can be viewed much weight to the meeting and their privileges including the right to host annual on the ASI website. participation was a forerunner of more scientifi c meetings of ASI every seven years extensive future collaboration. in rotation with the State Branches. Moreover, Conscious of the huge distances between affiliated, as opposed to amalgamated, Australian capital cities, in the early 1980s The procedure for setting up the members would not have voting rights and Council decided to establish State councillors early meetings of the New Zealand would be required to pay a capitation fee as to function primarily as a point of reference Immunology Society (NZSI) entailed did members of other affi liated organizations for Council distribution of information simply agreeing which centre should such as ASCIA. particularly relating to Annual Conferences. hold the meeting for the following year In 1991, Geoff Shellam, the then President, and choosing the President and organizer Following this correspondence, Roger Booth moved to create State branches of ASI to from that location. An Australian visitor advised in June 1991 that there was now provide a forum for immunology throughout was generally invited to attend these almost unanimous support amongst NZ the year. These branches, which also include meetings. members to proceed with amalgamation. New Zealand, operate via a Management Meetings in July fi nalized the principles Committee comprising a Chairman and In 1981, Jim Watson returned from the of amalgamation, including changes in the other such offi cers as is deemed necessary. University of California at Irvine to constitution and the name of the society. The regional councillor is a member of the take up the Chair of Microbiology in The ASI Executive insisted, however, that Management Committee but not necessarily Auckland. He supported the feeling that it it would only be appropriate to change its Chairman. The task of the Management was time to establish joint meetings with the name of the Society if the majority of Committee is to further the aims and the ASI. Consequently, the fi rst combined members of the current NZ Society joined objectives of ASI Inc. at the local level by meeting was held in Queenstown, NZ, ASI. These changes were accepted by postal (a) holding regular scientifi c meetings, (b) in December 1985. This meeting was vote of a 75% majority of members of ASI providing an organizational structure to organized by Barbara Heslop, as the and ratifi ed at the AGM of the Society held facilitate the visit of ASI sponsored speakers, President in Dunedin, with the help of in Perth in December 1991, the new Society (c) encouraging an increase in membership a committee consisting of Margaret being called the Australasian Society for in ASI by recruiting members locally and (d) Baird, Frank Griffen, Bruce Gibbons Immunology. co-ordinating all of the activities relating to and Mark Bradley. It was generally holding the annual scientifi c meetings of ASI accepted that this worked particularly Clearly, amalgamation with our New Zealand and the associated AGM when his/her city well and consolidated the idea that the colleagues has strengthened the Society and hosts these events. The move to consolidate two societies should become more closely the proposed benefi ts of the merger have the activities of State councillors has been associated. been largely fulfi lled. very successful, providing a functional body in each State and in New Zealand to This led in early 1991 to the opening of Administration promote awareness of the discipline and discussions concerning the possibility of form the necessary operating structures. State the two societies cementing the relationship During the 1970s the Australian Society councillors are full members of Council of either in terms of an established affi liation for Immunology, notwithstanding its ASI Inc. enjoying full voting rights. or as an amalgamation. In April 1991, formalization by the creation of a constitution, Roger Booth, the President of NZSI, was still a small affair run largely by voluntary Burnet Oration expressed uncertainty in the response labour. With the increase in membership and of NZ members to amalgamation, affi liation with other professional bodies In recognition of the outstanding contribution particularly as it would require signifi cant in the 1980s, the Society appointed Fay of Sir Macfarlane Burnet to immunology, constitutional changes to the NZ Turner to the role of part-time Executive which culminated in the award of the Society. Offi cer in 1980 and through her dedication Nobel Prize in 1960, Council created the

8 ASI Inc. Newsletter June 2011 annual award of ‘Burnet Orator’ in 1986. of the ‘Adelaide Journal’, approached the Features. A simple formula for Special The recipient of this honour, him/herself ASI Council with the proposal that the Features was developed which proved an outstanding immunologist, was required ‘Adelaide Journal’ change from being a to be very successful. The fi rst Special to present at the Annual General Meeting general medical/biology publication to being Feature was published in 1993 in the of the Society a major, general dissertation a journal focusing on immunology and cell October issue of ICB and covered ‘Recent which related to his or her area of expertise. biology. It was proposed that the name of Developments in Veterinary Vaccines’. It was eminently appropriate that Gus Nossal the journal be changed to Immunology and Since then, ICB has usually published presented the inaugural Burnet Oration at the Cell Biology (ICB), to refl ect this change three Special Features each year and by AGM in Newcastle in 1986. in content, and that it should become the the end of 2010 had published 59 Special offi cial journal of the Australasian Society for Features containing 300+ articles. A list of Burnet Orators and the topics of Immunology. The journal would, however, their presentations is available from the continue to be owned by the University There is no doubt that the Special ASI website. of Adelaide, with Blackwell Scientific Features increased the visibility of the Publications handling the publishing of ICB. journal, with the impact factor of ICB Honorary Life Members It was also suggested that ASI should have the climbing above 2 for the fi rst time in right to nominate members of the Editorial 2000. However, over the next fi ve years In 1980 Council decided to recognize Board. The ASI accepted this proposal and the ICB impact factor and the rate of the outstanding contribution of selected even agreed to underwrite any fi nancial manuscript submissions remained static, members, over several years, to the Society losses if they occurred. Thus, the fi rst issue with the receipt of enough high-quality by creating Honorary Life Memberships. of the new incarnation of the ‘Adelaide papers for publication continuing to be It was eminently appropriate to appoint, in Journal’ was published in February 1987. a serious issue. One encouraging feature 1981, Derrick Rowley the inaugural Life Ieva Kotlarski became the fi rst Editor-in- during this period, however, was that Member as he had played such an important Chief of ICB and Derrick Rowley, the last consistently 75–80% of unsolicited role in creating the Society. Editor of the ‘Adelaide Journal’, continued articles submitted to ICB originated from as the Deputy Editor. non-Australasian laboratories, indicating A list of Honorary Life Members, in the the international nature of the journal. In chronological order of their appointment, Despite initial excitement over the addition, this period established ICB as is available from the ASI website. establishment of ICB and ASI gaining its consistently one of the leading scientifi c ‘own’ scientifi c journal, submission of papers journals in the Asia-Pacifi c region. This The ASI’s Journal: Immunology and to ICB steadily declined during the next few high regional status resulted in the Nature Cell Biology; Chris Parish years. Australasian immunologists were not Publishing Group (NPG) approaching the willing to submit their papers to ICB and few Editor-in-Chief in 2005 and proposing Immunology and Cell Biology has a long immunologists in other countries showed that ICB be published by NPG. The ASI and illustrious history. It was founded as much interest as well. Council enthusiastically embraced this the Australian Journal of Experimental proposal and in 2007 publication of the Biology and Medical Science in 1924 by By 1992, when Chris Parish took over as journal was transferred from Blackwell the University of Adelaide. Over the next the Editor-in-Chief, the submission rate Publishing Asia to NPG. few decades the ‘Adelaide Journal’, also had declined to an alarming level such that affectionately known as “Possum’s Pages”, it was diffi cult to obtain enough quality The move to NPG dramatically increased became a well-respected international articles to fi ll each of the six issues published the visibility of ICB. There was also an journal. This was due to many of Australia’s annually. It was clear that drastic measures increase in the number of issues each leading biological and medical researchers were needed. Immediately after taking up year from 6 to 8 and a revamped and at that time contributing manuscripts to the the position, Chris Parish introduced a new more international Editorial Board was journal. In fact, between 1925 and 1972 Sir category of manuscript, the Theoretical appointed. Several new article types were Macfarlane Burnet published over 90 papers Article, and wrote a personal letter to almost also immediately introduced, the most in the journal. 200 immunologists worldwide inviting important being ‘News and Commentary’ them to contribute theoretical papers to the articles that have a similar format to the During the 1970s and early 1980s there were journal (this was the era before email!). well known ‘News and Views’ articles in frequent discussions amongst Australian A considerable number of high profi le Nature journals. Carola Vinuesa agreed immunologists about the possibility of scientists eventually submitted papers. Chris to act as the inaugural N&C Editor and establishing a new, Australian-based, also wrote an article for the ASI Newsletter Stuart Tangye joined her as an additional immunology journal as immunology had in which he ranked Australasian research N&C Editor soon after. By the end of become such a strong research discipline institutes for their support for the journal. 2010 already over 80 N&C articles had in Australia. The establishment during this Most major research institutes undertaking been published by ICB. Initially these period of a number of new international immunological research scored very poorly articles discussed high impact papers immunology journals, such as the European and were strongly encouraged to lift their recently published by other journals, such Journal of Immunology, the Scandinavian game. as Nature Immunology and Immunity, Journal of Immunology and Cellular but as the quality of ICB manuscripts Immunology, highlighted this point. In the The most important innovation that Chris improved, N&C articles began to feature mid-1980s Ieva Kotlarski, the Deputy Editor introduced, however, was the Special ICB articles.

9 ASI Inc. Newsletter June 2011

A new article type, the ‘Outstanding Immunology and Cell Biology in 1987 it fi nancially viable, despite the global fi nancial Observation’, was established in still remained the property of the University crisis in 2008–2009, the ASI now receiving 2007 with the aim of giving ICB a of Adelaide. By the early 1990s, however, $50,000–$80,000 per annum from NPG as unique identity to separate it from there was a strong view amongst ASI their share of the journal’s income. other immunology journals. This new Council members that, since ICB was the manuscript category captures research offi cial journal of ASI, the Society should A number of changes are planned for the articles in immunology which describe own the journal. As a gesture of support journal in the near future to handle the striking observations that have extremely for the journal, in 1992 ASI incorporated a substantial increase in submitted papers. In important conceptual implications compulsory hard copy subscription to ICB in 2012 the number of issues published each but do not delineate the underlying its membership dues. This practice continued year will increase from 8 to 10, with monthly molecular mechanisms involved. At the until 2007 when NPG replaced the hard issues being a likely possibility in the next few time, it was hoped that the new article copy subscription with an electronic one, years. The editorial make-up of the journal type would combat the worrying trend as well as free electronic access to a range has changed in 2011, with the Editor-in-Chief amongst the top scientifi c journals to of Nature journals. being assisted by three new Deputy Editors. refuse to publish novel fi ndings if they Chris Parish has retired as the Editor-in-Chief did not contain a detailed description of When Geoff Shellam (1991–1992) and and Gabrielle Belz has been appointed as molecular mechanism, even when the Roland Scollay (1993–1994) were serving the new Editor-in-Chief, although Chris observations reported obviously had as the ASI President, informal ownership will continue as one of the Deputy Editors far reaching implications for the fi eld. negotiations began with the University of during 2011. With the revamped editorial At the time of writing (October 2010), Adelaide. Negotiations were complicated by arrangements, increased rates of manuscript the ‘Outstanding Observation’ articles the fact that Blackwell Scientifi c Publications submissions and increasing numbers of have already been warmly received by were keen to purchase the journal for a issues, ICB is poised to become even more the immunology community, with 19 tidy sum and that Blackwell Scientifi c was prominent in the fi eld of immunology in extremely high-quality articles in this willing to consider joint ownership with future years. category being received and published ASI. Both of these arrangements were not by ICB. acceptable to ASI as they would result in ICB Special Interests Groups (SIG) being associated with the same publisher The net result of all these changes was a indefi nitely. In 1997 the ASI established a As the ASI developed it became apparent dramatic improvement in the ICB impact subcommittee, comprised of Anne Kelso, that the discipline was very diversifi ed, factor and ranking. The 2009 impact Geoff Shellam and Chris Parish, to negotiate covering a range of specifi c interests that were factor reached 4.200, which represented a deal with the University of Adelaide. It unique to various groups of immunologists. a >200% increase over the 2005 value. took another two years to broker a deal but, Accordingly, Council considered during an The ranking of ICB within the cohort of thanks largely to the efforts of Anne Kelso, in Executive Committee Meeting in 1991, the ‘Immunology’ journals also improved 1999 the University of Adelaide transferred possibility that these interest groups should dramatically. In 2005 ICB was ranked 76th the ownership of ICB to ASI for the princely form their own specialist bodies while still of 115 ‘Immunology’ journals, whereas sum of $1! remaining within the orbit of the ASI. The fi rst in 2009 the ICB ranking had jumped to of these was the Clinical Immunology Group 28th of 128 recognized ‘Immunology’ • Impact of the ‘Adelaide Journal’/ICB (CIG) which predated this 1991 meeting publications. The ICB performance on the Field of Immunology since it was formed in 1982. The Mucosal was also impressive when compared Over the last 86 years numerous important Immunology Group was formed in 1992, with other immunology society-based immunology papers have been published the Infection and Immunity Group in 2008 journals. Thus, ICB had a much higher by the journal, many of these classic papers and the Tumour Immunology Group, known ranking than the Scandinavian Journal being published before the ‘Adelaide Journal’ as the Tumour Immunology Workshop, in of Immunology (90th, Scandinavian became Immunology and Cell Biology. 1998 following a ‘one-off’ meeting in 1996. Society for Immunology), Immunology In fact, it could be argued that, based on Attempts to activate members of ASI with (47th, British Society for Immunology) this performance, ICB is the second oldest special interests in other related fi elds such and International Immunology (45th, immunology society associated journal in as Behavioural Immunology, Reproductive Japanese Society for Immunology) and the world, only eclipsed by the Journal Immunology, and Neuroimmunology to was approaching the ranking of the of Immunology that was founded by the form SIGs have not been successful to date. European Journal of Immunology (24th, American Association of Immunology in Unfortunately, the formation of the Cytokine European Federation of Immunological 1913. A list highlighting some of the most Research Association independent from the Societies) and the Journal of Immunology important immunological publications can ASI prevents this active and important aspect (22nd, American Association of be found on the ASI website. of immunology from being included in the Immunologists). Other criteria also ASI SIGs. indicated that the stocks of ICB were • ICB Future Prospects on the rise. The future of Immunology and Cell Biology It was proposed during the Executive looks very bright. The journal has now Committee Meeting of 1991 that recognition • Ownership of Immunology and Cell become fi rmly established as a leading of the SIG could take the form of limited Biology publication in the fi eld of immunology. Due financial assistance from ASI and the When the ‘Adelaide Journal’ became to its high stature, ICB has also remained very assistance of the Secretariat in providing

10 ASI Inc. Newsletter June 2011 names of potential members of that special powers to negotiate with the Colleges and activities and personnel involved in the interest group to facilitate interaction. government on clinically related matters. fi eld. In the case of ASCIA, it has brought Special interest groups would be encouraged In further support of this decision, Council clinical immunology and allergy together to conduct meetings as satellites of the resolved during its meeting in 1976 that and provided a respectable professional annual national ASI meetings, which might consideration should be given to holding home for the latter; it has also ensured infl uence the selection of some invited ASI the next workshop on allergy and that an that the clinical discipline is properly speakers. SIGs would forward a report of invitation should be extended to members of represented at government and College their activities annually to Council and these the College of Allergists to attend both the levels to the benefi t of both societies. would be published in the Newsletter. workshop and scientifi c meeting of ASI. They would also be invited to join the ASI if they • Mucosal Immunology Group • The Clinical Immunology Group felt it would be an appropriate body. It was Special Interest Group (CIG); Tony Basten resolved at the Council Meeting of 1981 to A brief, but comprehensive, history of When ASI was established, immunology as discuss the potential co-operation between the Mucosal Immunology Group was a recognized clinical speciality did not exist. the College of Allergists and the ASI. published by its founder, Allan Cripps, There were, however, two immunopathology in the ASI Inc. Newsletter of December units located in Melbourne at the Walter and Despite these initiatives, some clinically 2010 and is reported in part here. (Ed.) Eliza Hall Institute and the Alfred Hospital focused senior members of the Society felt headed by Dr Ian Mackay and Professor that their interests were not being adequately Early in 1992, the ASI raised the concept Richie Nairn respectively. The former was catered for and, headed by Roger Dawkins, of establishing special interest groups more clinically orientated with the focus set up a discrete Clinical Immunology Group with discussions occurring between on autoimmune liver disease, while the in 1982. This led to a vigorous debate among Geoff Shellam and Allan Cripps about latter dealt more with immunopathology the immunological community resulting in the possibility of an SIG in mucosal per se. The practice of allergy was separate the merging of the fl edgling CIG with the immunology. and overseen by the Australian College of ASI’s standing committee in 1983 with the Allergists. name of CIG being retained. The new CIG With support from Roger Booth who rapidly took responsibility for representing chaired the ASI organizing committee The early 1970s saw the development the speciality of clinical immunology (now for the Auckland meeting in 1992, of clinical immunology services across incorporating allergy) during negotiations the Mucosal Immunology Special the country, some of which encompassed with government and the Colleges over Interest Group (MI-SIG) was formed immunopathology testing and/or allergy. In the training programmes, fee setting for in December 1992. A Symposium on recognition of the need for a formal training immunopathology tests and quality control Mucosal Immunology was held and program spanning clinical immunology of diagnostic laboratories – all recognized Jerry McGhee from the University of and allergy, the Royal Australasian College functions of other clinically oriented Alabama at Birmingham and the then of Physicians and the Royal College of speciality societies. The formal title of CIG President of the International Society Pathologists of Australasia established three was established at the AGM of the ASI in for Mucosal Immunology gave an ASI diplomas, one each in immunopathology and 1984 as the Clinical Immunology Group plenary lecture. The prominence given clinical immunology (including allergy) with of the ASI, a title that would appear on its to mucosal immunology at the Auckland the third (and most popular) being a conjoint letterhead for all correspondence. The CIG ASI meeting was a great launch for the diploma from both colleges. was requested to report to ASI at the annual MI-SIG. Over 50 people attended the Council Meeting and the AGM and to forward fi rst AGM and the membership was The focus of ASI during this period was copies of relevant correspondence to the established. The principal goals of the on promoting basic immunology as one of Secretary of ASI. MI-SIG developed at this meeting area Australia’s strongest research disciplines, as follows: rather than its clinical aspects or for that matter In retrospect, the initial retention of CIG allergy. Consequently, the annual scientifi c under the umbrella of ASI was the right (1) To provide a forum for mucosal meeting did not cater for the interests of the strategy to adopt while the clinical speciality immunologists to meet through broad church of clinicians involved in the matured; however, ultimately and due in workshops and symposia to advance applied aspects of the fi eld. Nevertheless, the no small part to its success, CIG became the research of mucosal immunology Council of ASI as early as 1972 did move to the launching pad for an independent entity through debate and collaboration; establish a subcommittee to liaise with the in the form of the Australasian Society (2) To be recognized as a specialist group Royal Colleges over provision of training for Clinical Immunology and Allergy within the ASI and to create a formal courses in clinical immunology. Convened (ASCIA). This concept of amalgamating association with the International by Richie Nairn, this subcommittee included the CIG with the Australasian College of Society for Mucosal Immunology; Ian Mackay, David Nelson, Ron Penny and Allergy was discussed during the AGM and John Sands (representing the Colleges) of the ASI in 1991, a feat requiring even (3) To organise a network of Australian and by the next annual meeting had more tact and diplomacy than was needed and international researchers in the prepared a comprehensive report on training for the CIG and taking the best part of fi ve fi eld of mucosal immunology. requirements. Following acceptance of the years. Importantly, both societies are now report by ASI, it was converted into a full fl ourishing in parallel and between them Over the years the MI-SIG has continued standing committee and accorded executive are catering well for the expanded range of to provide a forum for mucosal

11 ASI Inc. Newsletter June 2011

immunologists and colleagues with Currie) and New Zealand (Roslyn Kemp). in cancer, as it provided a new forum associated interests to meet at ASI Infection and Immunity also launched their dedicated to their topic of interest. The idea symposia and workshops as well as a website in early 2009 (www.iiasi.org). of a meeting devoted to ‘immunology and number of mini-symposia organized cancer’ was driven from the belief, prevalent around international visitors. While Infection and Immunity was a at the time, that the broader ASI community relatively new SIG, it gained immediate only infrequently dealt with the topic and At the eighth International Congress of popularity amongst ASI members and had the related issue of immune-based cancer Mucosal Immunology (ICMI) held in attracted almost 60 affi liate ASI members therapies. Given the controversy and lack of San Diego in 1995, Allan Cripps and his by ASI2009. Continued expansion and consensus on the immune response to cancer MI-SIG colleagues won the bid to host interest from ASI members attracted almost over the previous several decades, perhaps the ninth ICMI in Sydney in January 100 members within a year. The Infection this was not surprising! 1997. Allan and the late Graham Jackson and Immunity SIG Workshop organised by were appointed by the MI-SIG to co- Matt Sweet (Queensland representative) The early 1990s saw a major rekindling chair the 9ICMI organizing committee. at ASI2009 Gold Coast attracted over 80 of interest in tumour immunology, driven This meeting, with over 1000 delegates, participants, attracting the highest attendance largely by two factors: fi rst, molecular was the high spot for the MI-SIG. of all the SIG workshops organised, again and cellular immunology techniques The success of this meeting and the demonstrating the popularity of the SIG. The had unequivocally demonstrated that international acclaim that it brought for program for the workshop was bolstered by certain human malignancies (particularly Australian researchers in the mucosal the involvement of Paul Kaye (UK), one of melanoma) are immunogenic and that immunology fi eld demonstrates without ASI2009’s international invited speakers circulating cytotoxic T cells directed against a doubt the value of strong special who generously gave up his time to also tumour antigens could be isolated and interest groups within the ASI. speak at the SIG. He was ably supported by expanded, and, second, the fi rst dendritic cell national invited speakers Chris Engwerda, vaccines were being applied to human disease The MI-SIG has made a very substantial Richard Ferrero, Michael McGuckin, (particularly cancer), providing the hope of a contribution to the ASI community over Andrew Brooks and Mariapia Degli-Esposti. cellular adjuvant that might prove effective the past two decades through workshops, A similar workshop was held at the ASI2010 in augmenting the response of vaccinated symposia and more recently full-day Perth meeting. patients to synthetic tumour antigens with satellite meetings. It has also supported which the DCs had been pulsed. young researchers through awards and Infection and Immunity also organised a travel grants to attend conferences. very successful joint session at ASI2009 The fi rst ‘offi cial’ TIW was held in association Allan retired as the MI-SIG Chair at the with the Mucosal Immunology SIG which with the 1998 Melbourne ASI conference, end of 2009 having served in this role was headed by Brian Kelsall and Philip and was jointly organised by Geoffrey for 15 years of the MI-SIG’s 18-year Hansbro. This co-operation between the SIGs Pietersz, Mark Smyth and Joe Trapani at existence. has continued such that the joint session is the suggestion of Bruce Robinson and Ian an ongoing feature of the SIG workshops at MacKenzie. The conference worked well, • Infection and Immunity Group ASI annual meetings. as the workshop attracted well over 100 Ashley Mansell registrants and several international guest The Infection and Immunity SIG was Despite its recent beginning, the Infection speakers. This meeting was also the occasion offi cially accepted by the ASI executive and Immunity SIG has become involved of the inaugural Gordon Ada oration, which in October 2008 following a proposal in local branch activities and organization to today recognises an Australian tumour to ‘… provide a forum and focus for of ASI events as a means of promoting and immunologist considered to have made researchers from across different fi elds of highlighting the research, collaborative important contributions to the fi eld. At the interest to interact and collaborate on the efforts and profi le of the SIG. Infection and Melbourne 1998 meeting, Professor Gordon common interest of immune recognition Immunity is actively playing a role in the Ada presented the fi rst of these orations, on and response in both immunological organization of current ASI annual meetings the topic of AIDS, the immune response and directions: innate and adaptive’. The aims and will continue to provide a forum for ASI cancer development. of the SIG were to provide an opportunity members with an interest in host:pathogen to further enhance and develop research interactions and infection and immunity. The TIW has continued to fl ourish since that within ASI to understand the ‘ritualistic Infection and Immunity SIG currently has 96 seminal fi rst meeting, having complemented dance’ between host and pathogen ASI members as affi liate members (2010). every ASI meeting to the present day. The interactions. ‘timing’ of this series of meetings could not • Tumour Immunology Group; Joe have been better, given the massive amount A committee was formed, with Ashley Trapani of activity in this area of research, and the Mansell as the inaugural chair (and The Tumour Immunology workshops plethora of associated clinical trials over Victorian representative) in addition to (TIW) of ASI commenced formally in 1998, the past decade. The TIW has no formal representatives from nearly all ASI state following an initial ‘one-off’ meeting in 1996 standing committee and each workshop branches: Queensland (Matt Sweet), organised by Bruce Robinson and held in is organised by an adhoc committee of NSW (Nick Gorgani), South Australia association with the ThymOz meeting of interested scientists and clinicians from (Susanne Heinzel, replaced by Erin that year. The 1996 meeting was seen as the ASI host city. In general, the TIW has Curry), Western Australia (Andrew highly useful by immunologists interested occupied the greater part of the opening

12 ASI Inc. Newsletter June 2011 day of each ASI meeting. CSL Limited has and Peter Doherty (2007–10) have held of ASCIA and both Societies attempt to generously provided fi nancial support for the the offi ces of President of IUIS following hold their annual scientifi c meetings to TIW since its inception. Along with modest appointment as Vice-President in 1983–86 coincide if possible. registration fees, CSL’s support has typically and 2004–07 respectively, Anne Kelso held enabled at least two renowned international that of Secretary General for the triennium ASI Inc. Newsletter speakers to present their work at TIW and 1998–2001 and Nick King was elected to cover a separate topic at the associated IUIS Treasurer in 2010. In addition the The ASI Newsletter began informally as ASI meeting. Apart from Gordon Ada, other Australasian Society has been represented a quarterly news sheet sent out by Fay Ada orators have included Ian Frazer, Denis by elected councillors since the inception Turner when she was appointed Executive Moss, Chris Parish, Chris Schmidt, Bruce of IUIS. Offi cer in 1980. When the Society’s Robinson, Ian MacKenzie, Jonathon Cebon, business was handed over to the Victorian Mark Smyth, Peter Hersey and Joe Trapani. • FIMSA Postgraduate Medical Foundation in Mac Burnet would be very pleased to have The Federation of Immunological Societies 1984, Dick Briggs temporarily took seen the TIW become such a feature of ASI, of Asia–Oceania (FIMSA) is a non-profi t responsibility for the Newsletter with given his seminal contribution as an architect organization founded in 1992 to advance, by the help of the then current Honorary of the cancer immune surveillance. holding workshops and educational programs Secretaries. Dick expanded it and and holding congresses every 3–4 years, the accepted paid advertisements. It was Association with other organizations science of immunology in the Asia–Pacifi c then administered by a series of editors, both internationally and nationally region. All immunological societies and who like the ICB Editor-in-Chief are associations within the Asia–Pacifi c region non-voting member of Council. With its growth in membership and function, who are members of IUIS are eligible to the Society felt the need to become associated become members of FIMSA. The ASI is a The newsletter has become a forum with other organizations with which it founding member of FIMSA and hosted and for discussion of ASI news and shared professional interests, particularly organized the fi rst FIMSA Congress which views, particularly those presented in immunology. Foremost of these is the was held in Adelaide from 1 to 5 December in the President’s Report, publicizing International Union of Immunological 1996. forthcoming immunological seminars Societies (IUIS). lectures and conferences and local • ASMR or international meetings, providing • IUIS The Australian Society for Medical Research information on major events held by IUIS was founded at a meeting in Brugge, (ASMR), established in 1961, is the peak the various branches, reviewing books, Belgium, on 5 May 1969 by the representatives professional society representing Australian and advertising job vacancies and of ten Societies. The Australian Society of health and medical research. ASI is one of fellowships. It is published quarterly and Immunology was not represented but the 57 affi liated professional societies and plays an important role in the effective expressed support and later was accepted Medical Colleges which together comprise running of the Society. as a founding member after it had created 100,000 Australians actively engaged in a constitution. health and medical research within the Summary ASMR network. There are currently 54 Member Societies of From the early informal gathering in IUIS, many of which belong to one of four • ANZCCART Adelaide in 1962 of eleven practising Regional Federations encompassing Europe, The Australian and New Zealand Council immunologists and a few PhD students, Latin America, Africa and Asia-Oceania. for the Care of Animals in Research and ASI Inc. has grown dramatically into a Teaching (ANZCCART) was established vigorous society of 1012 (as of December International Congresses of Immunology to inform scientists and teachers of the 2010) members from both Australia (ICI) are held in different locations every technical and ethical issues relating to the and New Zealand. In so doing ASI Inc., three years under the auspices of IUIS. The use of animals in research and teaching. together with its own scientifi c journal, fi rst ICI was held in Washington in August ASI is a full member of ANZCCART. has earned its just place amongst the 1971 and the third in Sydney in July 1977 leading international immunology where Geoff Cooper functioned brilliantly • ASCIA societies. as General Secretary. This Congress, which The Australian Society for Clinical 600 registrants attended, marked Australia’s Immunology and Allergy (ASCIA) was This rapid expansion of numbers for coming of age immunologically. The 16th ICI formed in 1990 by merging the Clinical a relatively small country refl ects the will be held in Melbourne in 2016 following Immunology Group of ASI with the emergence of the discipline, or rather our a successful bid by a committee chaired by Australian College of Allergy. While the CIG recognition of it, as playing a central role Jose Villadangos. was a Special Interest Group of ASI, ASCIA in most aspects of medical and veterinary emerged as a separate and highly successful science. In the 1960s and early 1970s we Australasian immunologists have, since Society with its own constitution and were struggling to understand the nature its inception, given strong support to governance although both bodies maintain and characteristics of antibodies and the IUIS and to ICIs in particular, being well and foster the close and trusting relationship role of B and T cells in regulating the represented in attendance and on the scientifi c expressed at the inaugural meeting of ASCIA. immune response. Today Australians are programs. Both Gus Nossal (1986–89) Many members of ASI are also members researching widely diverse aspects such

13 ASI Inc. Newsletter June 2011

as molecular immunology, lymphocyte recognize target antigens in combination to the many colleagues and friends who traffi c, MHC restriction, monoclonal with major histocompatability complex supported me during the exciting years of antibody therapies, immunogenetics, (MHC) proteins. These three outstanding membership in ASI Inc. of which we should cytokines and chemokines and members of ASI Inc. should serve as role all be proud. speculating on how these new tools and models for current and future members of concepts might be applied to the control the Society. The following documents can be viewed and eradication of disease. Pity the poor on the ASI website (www.immunology. veterans of my era to whom these studies Acknowledgements org.au) constitute a foreign language. I express my appreciation to many Appendix 1 The Society is honoured that three of its colleagues who assisted in providing relevant Constitution of the Australasian Society for most outstanding members, Sir Frank information, patiently putting up with my Immunology Macfarlane Burnet, Peter C. Doherty and persistence and unreasonable demands Rolf Zinkernagel have been made Nobel for instant attention in providing same. In Appendix 2 Laureates. Macfarlane Burnet and Peter particular thanks are due to Susanne Heinzel Offi ce bearers of ASI and meetings Medawar were co-recipients of the 1960 and Judith Greer for their numerous, mostly Nobel Prize in Physiology or Medicine successful attempts to provide information Appendix 3 for demonstrating acquired immune from almost non-existent archives. Thanks Burnet Orators and their topic of tolerance, research that provided the are also due to Geoff Shellam for providing presentation experimental basis for inducing immune a comprehensive collection of documents tolerance, the platform for developing concerning the period when he functioned as Appendix 4 methods of transplanting solid organs. President and for his support. The sectional Honorary Life Members of the Society Peter Doherty’s research focuses on how authors, Tony Basten, Chris Parish, Allan the body’s immune cells protect against Cripps, Ashley Mansell and Joe Trapani, Appendix 5 viruses. He and Rolf Zinkernagel, the made my task much easier by producing Some of the most important immunological co-recipients of the 1996 Nobel Prize in excellent reviews of their areas of particular publications that appeared in Immunology Physiology or Medicine, received their interest and I am appreciative of their and Cell Biology award by demonstrating how T cells support. Finally, I express my sincere thanks

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14 ASI Inc. Newsletter June 2011 ASI COUNCIL – WHAT IT IS AND WHAT IT DOES

As an ASI member you’d have had some Speaker Program co-ordinator (Alejandro of the day-to-day tasks are delegated to dealings with the ASI Council, be it through Lopez), the website administrator (Judith the Executive to deal with between the applications for awards, the visiting speaker Greer), the Day of Immunology co-ordinator meetings. Therefore, with accepting program, emails from the Secretary, reading (Delia Nelson), the meeting co-ordinator the mandate of being member of ASI the reports from the Executive in the (Bernadette Saunders), the ICB Editor in Executive, one also accepts responsibility newsletter or possibly some other occasion. Chief (Gabrielle Belz) and the FIMSA (Guna not only for the specifi c position being I’d imagine that many of you would have Karupiah and Nick King) and IUIS (Franca fi lled, but also for playing a major part in wondered at some stage during your Ronchese) representatives. Our thanks go the decision making of general matters membership how the Council is structured out to these individuals who do an enormous (and, with that, for a quite substantial time and what it means to be a member of the ASI amount of work in the background. commitment). Likewise, with acceptance Council or Executive. of the position as a Branch Councillor, one The mandate given to the voting Council also accepts membership of ASI voting The members of ASI voting council are is defi ned in the ASI Constitution and I’ve Council with all its responsibilities and elected by membership. As it happens, attached an extract of the Constitution at rewards. there are a number of Council positions the end of this article. The full Constitution coming up at the end of the year, including can be viewed and downloaded from the Being an ASI Councillor can open up two positions on Executive (Hon Secretary ASI website. many opportunities. Council positions are and Vice President) and the NSW Branch staggered so that any new Councillor will Councillor. The Council is ultimately responsible for always join a group of people with one or the Society and its members. It remains in two years in the job who are willing to help In this article I’ve tried to shed some light Council’s hands to ensure that the Society and share their experience. It is a great onto the governance of ASI, as this is the is fi nancially viable and to make decisions way to network and learn more about the mandate given to the Councillors by the on how to redistribute membership fees and immunology done in Australia/NZ. It’s a membership through the elections. other income for the maximum benefi t to our great addition for anybody’s CV and one members. It is also responsible to advance not only gets a chance to ‘meet the locals’ To understand how the Council operates our discipline and to support and engage our but Councillors also get to interact with it’s probably best to fi rst introduce the members wherever possible. the invited visiting speakers throughout composition/structure of the Council. The the year and at the annual meetings. ASI Council is made up by the ‘offi ce With being elected onto ASI Council, the bearers’ which are the President (currently Councillor assumes responsibility for the During my time on Council, fi rst as Dave Tarlinton), the Vice or the Past smooth operation of the Society. This includes SA/NT Branch Councillor and then a President (depending on which part of the day-to-day tasks but also involves decision few years later as Hon. Secretary, I’ve cycle we are in, currently this is the Past making on fi nancial and other activities. had the chance to meet and work with President, Miles Davenport), the Treasurer With the Society growing from strength to some fantastic people. It has been a great (Pablo Silviera) and the Secretary (myself). strength, we are responsible for increasing opportunity to learn from the best and Collectively the offi ce bearers are also fi nancial assets. The Society organises some to form some great collaborations and known as the ‘Executive’. Additionally we big events, evidently the biggest one being wonderful friendships. As one of our past have seven ‘Branch’ Councillors (often, the annual scientifi c meeting which often presidents recently said to me: ‘My time but incorrectly – as our NZ members quite has a budget in excess of $500,000. While on Council was one of the most rewarding rightly like to point out – also referred to these events are usually organised by local things that I have done throughout my as ‘State’ Councillors) representing WA, organising committees, it remains the duty career.’ And I couldn’t agree more. SA/NT, Vic/Tas, ACT, NSW, NZ and Qld. of the Council to ensure that money is spent Together, these 11 positions form the voting sensibly, budgets are reasonable and assets Susanne Heinzel Council and each of these positions is elected of the Society safeguarded at all times. Hon. Secretary by ASI membership. The term for each of those positions is three (3) years, except for ASI Council meets twice a year, at the the position of President, which is a total of annual Council meeting (ACM) usually just The mandate given to the voting Council four (4) years on executive: one year before prior to the scientifi c meeting and then also as defi ned in the ASI Constitution: (vice-president) and after (past-president), in May or June for the mid year Council ‘13. Council and the 2-year presidential term. meeting. During these meetings Council 13.1. The affairs of the Society shall be receives reports from its voting and non managed by a Council constituted as Additionally to the voting Councillors, we voting councillors, makes decisions on the provided in Rule 14.’ have an array of non voting Councillors who expenditure and spendings throughout the offer their time and expertise to the Society. year and makes plans for the years to come. It goes then on to explain that ‘council These include (in no particular order): the While all major decisions are made during shall control and manage the business Newsletter Editor (Simon Apte), the Visiting these council meetings, for simplicity many and affairs of the Society’ ‘exercise all

15 ASI Inc. Newsletter June 2011

such powers and functions...... other Quick Fire Immunology Series at QIMR than those powers and functions that are required by these rules to be exercised by general meetings’ and ‘subject to these In an effort to build the profi le of immunology at QIMR, Ash Haque (ASI State Councillor, rules, the regulations and the Act, has Qld), and his colleagues from Chris Engwerda’s Lab organised what was hopefully the power to perform all such acts and things fi rst in an ongoing series of special lunchtime events. Speakers were given just ten minutes as appear to the Council to be essential for to impress the audience with their angle on the virtues of immunology. Geoff Hill got the proper management of the business the ball rolling with his talk entitled “Immunology is not gobble-dee-gook” (which was and affairs of the Society’. in response to comments by an eminent local biochemist), followed by Chris Engwerda, Corey Smith, Michelle Wykes, Kelli MacDonald, Denise Doolan, and Ash Haque. The It also states: event was extraordinarily well patronised, not just because of the great immunology, but 15.2. The Council may delegate to possibly due to the free gourmet burgers prepared by the Engwerda Lab! the Executive Committee the power to carry out the day-to-day business of the Society. The Executive Committee shall be answerable to Council and shall report to Council annually or as otherwise requested by Council. Notwithstanding the foregoing, the Council may put budgetary limits on expenditure by the Executive and before making major expenditures the Executive must obtain Council approval.

LtoR: Fiona Amante, Fabian Rivera, Shannon Best: Geoff Hill: Chefs extraordinaire from the Engwerda Lab Immunology is not (Photo: Simon Apte) gobble-dee-gook (Photo: Alan Baxter) BIG Annual Retreat

The Brisbane Immunology Group will hold its Annual Retreat at the Sea World Resort, Gold Coast from August 18–19, 2011. Please note that accommodation options at the resort are limited, so register online as soon as possible to avoid disappointment.

Check out http://www.qimr.edu.au/ big/annual_retreat/annual_retreat.html Gourmet burger chefs Patrick Bunn (aka Tom Cruise) Corey Smith and Ash Haque for details on sponsors, meeting venue, (Photo: Simon Apte) (Photo: Simon Apte) accommodation, invited speakers and registration information.

Last date to register is JULY 8, 2011.

Kelli MacDonald: Chris Engwerda All roads lead to immunology (Photo: Simon Apte) (Photo: Simon Apte)

16 ASI Inc. Newsletter June 2011 Bursa of Fabricius at the Centre of Trans-Tasman Scandal

There is a new rift in the Trans-Tasman graph) indicates that Phil Hodgkin still leads relationship; and for a change, it’s not about the fi eld with a Bursa of Fabricius (BF) factor rugby or cricket, or Centrelink, funny accents, of seven, closely followed by Ian Frazer at Eskys, the number six, Russel Crowe, fi ve. It was good to see that Ovalbumin and thongs, Pavlovas, race horses, or sheep. No, Th17 were lower this year and I am reliably this time it is serious, it has to do with the informed that Barbara Fazekas is relieved to most prized giblet in history – The Bursa of also be lower this year. Fabricius Award. Kiwis Jo Kirman and Anne La Flamme won the Award at last year’s ASI So as it stands, the Bursa is still missing. conference in Perth with this: I will leave you with this classic Ode to The Bursa penned by Nick King and Lyn We propose a brand-new debate: Corcoran in 2003. New Zealand is not a state it’s true that we share I do want the B. of Fabricius the Queen and her heirs I can taste it and it is delicious but John Howard we did not create My best friend agrees It needs batteries The Kiwis claim that in the spirit of the But that might make my husband great underarm bowling incident of 1981, suspicious. the Aussies have cheated them out of Graph Legend. enjoying their prize by hiding the trophy NFI= unintelligible; at the last minute. This is not supported by NFWA=not funny the photographic evidence of the last known without alcohol; sighting, which clearly shows John Fraser BIFA= bits of Ian Frazer’s (NZ) beginning to sequester the trophy away anatomy from Lindsay Dent (Aus). This is supported by a photo that’s recently emerged that appears to show Anne La Flamme menacing Lindsay Dent with the Bursa. Personally I think a far more entertaining way of stopping Anne and Jo from enjoying the trophy would have been to let AQIS handle it at the airport.

The limerick competition has long been The Last Known Sighting with Lindsay Dent and John regarded as a weather vane for what’s hot in Fraser immunology. A quick analysis of the data (see (Photo: Alan Baxter)

Mystery Disappearance: The coveted Bursa of Fabricius (Photo: Alan Baxter)

Anne La Flamme with intent?

17 ASI Inc. Newsletter June 2011 THE ASI VISITING SPEAKER PROGRAM 2011

Forthcoming speakers conferences, as well as being awarded the Schwartzberg. 2007. Requirements for selection August: American Association of Immunologists of conventional and innate T lymphocyte lineages. Dr Pam Schwartzberg (AAI) BD Biosciences Investigator Award Immunity 27:775-785. National Human Genome Research in 2008 – this award recognizes outstanding, Institute, NIH, Bethesda, MD, USA early-career research contributions to the October: Visit co-ordinated by Stuart Tangye fi eld of immunology. Pam is an excellent role Professor Emil R. Unanue, MD (Garvan Institute) model for clinical immunologists/scientists, Washington University School of Medicine, and also for the many female members of St Louis, USA ASI. Pam has visited Australia previously as Visit co-ordinated by José Villadangos an invited plenary speaker at the ASI2007 (WEHI) annual conference held in Sydney, and she has collaborations with several research groups in Australia (ie in Sydney, Canberra and Melbourne). Her research interests overlap with those of many labs in Australia and NZ (i.e. lymphocyte development, Th cell differentiation, immune defi ciencies, role of cytokines, mouse models/gene-targeting, Pam is an MD and a Senior Investigator cell signaling etc). in the Genetic Disease Research Branch “We examine antigen processing and of NHGRI, NIH. Her research interests Selected Publications from the last three presentation by the antigen presenting cells focus on studying signal transduction years: (APC), and the interactions of CD4 T cells in T cells, in particular determining the E. K. Deenick, A. Chan, C. S. Ma, D. Gatto, P. with the peptide-Major Histocompatibility roles of signaling molecules that affect T L. Schwartzberg, R. Brink and S. G. Tangye. complex (MHC) proteins. The MHC cell function and their ability to respond 2010. Follicular helper T cell differentiation molecules constitute a protein system that to infection. This has been achieved by requires continuous antigen presentation that is rescues peptides from extensive intracellular generating novel strains of knock-out independent of unique B cell signaling. Immunity degradation. The class II-MHC molecules, mice, combined with state of the art 33:241-253. which we study, bind primarily to peptides technology such as 2 photon imaging, J. L. Cannons, J. Z. Wu, J. Gomez-Rodriguez, derived from the vacuolar digestion of microRNAs and deep sequencing. J. Zhang, B. Dong, Y. Liu, S. Shaw, K. A. Siminovitch and P. L. Schwartzberg. 2010. internalized proteins. The APC uses MHC- Over the past 10 years, Pam’s lab has Biochemical and genetic evidence for a SAP- molecules to present antigenic determinants made substantial contributions to our PKC-theta interaction contributing to IL-4 to the T cell system. understanding of the functions of the regulation. J Immunol 185:2819-2827. adaptor protein SAP, the kinases Itk, J. L. Cannons, S. G. Tangye and P. L. Schwartzberg. “We examine the processing and the features Btk and Rlk, and the cytoskeletal protein 2010. SLAM Family Receptors and SAP Adaptors of peptides that allow for their binding to WASp in lymphocyte development, in Immunity. Annu Rev Immunol. and selection for class II-MHC molecules. function and differentiation. This has J. L. Cannons, H. Qi, K. T. Lu, M. Dutta, J. For this we use the protein hen-egg white included providing important insights Gomez-Rodriguez, J. Cheng, E. K. Wakeland, R. lysozyme (HEL) and the listeriolysin O for the requirement for the generation N. Germain and P. L. Schwartzberg. 2010. Optimal germinal center responses require a multistage T protein, the major virulence protein of of specifi c lineages of lymphocytes, cell:B cell adhesion process involving integrins, Listeria monocytogenes. We are trying to their differentiation to specifi c T helper SLAM-associated protein, and CD84. Immunity identify the intracellular vesicles that contain lineages (Th1, Th2, Th17, TFH) and their 32:253-265. class II-MHC and their interaction with acquisition of effector function. J. Gomez-Rodriguez, N. Sahu, R. Handon, T. vesicles that bear the internalized protein S. Davidson, S. M. Anderson, M. R. Kirby, A. antigen. We correlate our biochemical These fi ndings are not only important for August and P. L. Schwartzberg. 2009. Differential fi ndings with the response of T cells. At the advancing basic science, but also have expression of interleukin-17A and -17F is coupled present time we examine: the biochemistry clinical relevance since several of these to T cell receptor signaling via inducible T cell of peptide selection, the T cell response genes are mutated in human primary kinase. Immunity 31:587-597. J. A. Readinger, G. M. Schiralli, J. K. Jiang, C. to various peptide-MHC complexes, immuno defi ciencies – i.e. SAP in X- J. Thomas, A. August, A. J. Henderson and P. L. conformational isomers of peptide-MHC linked lymphoproliferative disease; BTK Schwartzberg. 2008. Selective targeting of ITK and post-translational modifications of in X-linked agammaglobulinaemia, and blocks multiple steps of HIV replication. Proc peptides. WASp in Wiskott-Aldrich syndrome. Natl Acad Sci U S A 105:6684-6689. H. Qi, J. L. Cannons, F. Klauschen, P. L. Schwart- “At present, a major focus centres on The importance of Pam’s work is zberg and R. N. Germain. 2008. SAP-controlled the immunopathogenesis of autoimmune evidenced by many of her recent T-B cell interactions underlie germinal centre diabetes mellitus. Our studies on autoimmune publications that have appeared in high- formation. Nature 455:764-769. diabetes are attempting to identify the impact journals, her frequent invitations R. Horai, K. L. Mueller, R. A. Handon, J. L. Cannons, S. M. Anderson, M. R. Kirby and P. L. antigens from beta cells that activate both B to be a plenary presenter at international 18 ASI Inc. Newsletter June 2011 and T cells. We combine biochemical analysis involving mass spectrometry with cellular New Investigator Prize studies. Where is the antigen presentation Stacey Walters, Garvan Institute, Sydney fi rst taking place responsible for disease initiation? Which APC present diabetogenic BAFF, a B cell activating factor of the that thymic B cells may be involved in antigens? What are the antigens? How are TNF family, was originally known to be the negative selection of thymocytes. the beta cells recognized and how are they essential for B cell survival and maturation A notable feature of the thymic B cells affected by the immune process? Which T (1 & 2). However, there was some previous in BAFF-Tg mice was the increased cells cause diabetes? These are some of the published data showing BAFF might have frequency of cells that were B220Hi fundamental questions that are asked.” role for T cells where BAFF transgenic CD1d+. Combining data from BAFF-Tg, (BAFF-Tg) mice were found to have an wild type and µMT-/- mice we were able Selected Publications from the last 3 increase in CD62Llow and CD44hi memory to show that the expansion of thymic years: effector T cells in both the CD4 and CD8 T Tregs directly correlated to the amount of Atibalentja DF, Murphy KM, Unanue cell pool (3). Also, T cells stimulated with thymic B cells present. Indeed in BAFF- ER. Functional Redundancy between anti CD3 showed increased proliferation in Tg mice thymic B cells increased with age Thymic CD8{alpha}+ and Sirp{alpha}+ Conventional Dendritic Cells in the presence of BAFF (4). These observations as did thymic Tregs and this correlated Presentation of Blood-Derived Lysozyme led us to become interested in the role of with suppression of the graft rejection by MHC Class II Proteins. J Immunol. BAFF on T cells. response; resulting in ~80% allograft 2010 Dec 22. acceptance in 16 week old BAFF-Tg mice We went on to demonstrate in a murine versus 100% graft rejection in 6 week old Yang CW, Strong BI, Miller MJ, Unanue model of islet allograft transplantation, that BAFF-Tg mice. In contrast, aged wild ER. Neutrophils infl uence the level of over-expression of BAFF could directly type mice did not show increased thymic antigen presentation during the immune control T cell dependent immunity, in that B cells or Tregs and always rejected an response to protein antigens in adjuvants. the majority of BAFF-Tg mice accept the allograft. Together these data lead us JImmunol 2010 185(5):2927-34. islet allograft permanently. A series of to believe there is a direct relationship Mohan JF, Levisetti MG, Calderon B, experiments revealed this was due to BAFF between B cells, thymic Tregs and control Herzog JW, Petzold SJ, Unanue ER. promoting a ~3 fold expansion of Foxp3+ of T cell immunity; however I think I Unique autoreactive T cells recognize Tregs (5). Further to this, our data did not will be kept rather busy in the next few insulin peptides generated within the islets support a T cell intrinsic mechanism for months trying to nut all this out and fi nd of Langerhans in autoimmune diabetes, the expansion of Tregs in that the BAFF the ever elusive “mechanism”. Nature Immunology 2010 11: 350-354. dependant expansion of peripheral Tregs was shown to be B cell dependent. Last but not least I would like to thank Belizaire R, and Unanue ER. Targetting the ASI for giving me the opportunity to protein antigens to distinct subcellular Through further experimentation we found present my work in the Young Investigator compartments reveals unique molecular and proteolytic requirements for MHC class that BAFF was not enhancing Treg survival, session. I amd II presentation. Proc.Natl. Acad. Sci proliferation or conversion but rather BAFF- USA 2009 106: 17463-17468. Tg mice were found to have a ~3 fold increase References: in thymic Tregs. The observed thymic Treg 1. Batten, M., Groom, J., et al. (2000). Suri A, Levisetti, ML, Unanue ER. Do the expansion was lost in the absence of B cells “BAFF mediates survival of peripheral peptide-binding properties of diabetogenic and interestingly B cell null µMT-/- mice immature B lymphocytes.” J Exp Med class II molecules explain autoreactivity? exhibited a decreased frequency and number 192(10): 1453-66. 2. Mackay, F. and Browning, J. L. (2002). Curr Opinion Immunol 2008 20: 105-110. of thymic Tregs compared to wild type mice. “BAFF: a fundamental survival factor Collectively these data indicate a role for B Date City for B cells.” Nat Rev Immunol 2(7): cells in thymic Treg production. Interestingly, 3–4 October Sydney 465-75. histological analysis of BAFF-Tg mice 3. Mackay, F., Woodcock, S.A., et al. 5 October Canberra revealed large clusters of B cells as well as (1999). “Mice transgenic for BAFF 6 October Adelaide scattered B cells in the thymus, where as wild develop lymphocytic disorders along 7 October Melbourne type mice had only small scatterings of B with autoimmune manifestations.” J Exp 10 October Brisbane cells in the thymus and no clusters were ever Med 190(11): 1697-710. observed. Very generally, positive selection 4. Ng, L. G., Sutherland A. P., et al. (2004). “B cell-activating factor belonging to the of thymocytes occurs at the double positive TNF family (BAFF)-R is the principal stage and is mediated in the cortex of the BAFF receptor facilitating BAFF thymus by cortical epithelial cells, whereas costimulation of circulating T and B negative selection of thymocytes occurs in cells.” J Immunol 173(2): 807-17. the medulla region via interactions with DCs 5. Walters, S., Webster, K.E., et al. (2009). and medullary thymic epithelail cells. “Increased CD4+Foxp3+ T cells in BAFF-Transgenic mice suppress T cell We then went on to show the B cells in both effector responses.” J Immunol 182(2): BAFF-Tg and wild type mice were residing 793-801. in the medulla of the thymus, suggesting

19 ASI Inc. Newsletter June 2011

Jürg Tschopp (1951–2011) Andreas Strasser & Fabienne Mackay

It is with profound sadness that we have to eventually resulted in the formation of three inform the members of ASI that Professor biotechnology companies, testifying to his Jürg Tschopp, a close colleague of many eager entrepreneurship. scientists in Australia and an outstanding scientist, unexpectedly died on March One of Jürg’s most striking traits was his 22nd. He suffered a heart attack while constant attraction to unexplored fi elds of doing what he loved most, practicing biology. At the summit of his productivity sport in his beloved Swiss Alps with his on the TNF/TNF-R families and cell family. Jürg loved to escape to the rarefi ed death regulation, he already developed air of the high peaks of the Valais to be his future research focus by designing with his family after busy periods of a theoretical model, entirely based on work or travel giving seminars around predictions of protein-protein interactions, the globe. that proposed pro-IL-1β activation by Caspase-1 in a molecular complex, now Jürg was from Basel, Switzerland. He was termed “infl ammasome”. Since then, he an outstanding young athlete, nationally dedicated most of his thoughts and efforts ranked in the decathlon, and never lost to tackle this idea, which, after minor his athleticism and competitive spirit as adjustments, was described in 2002. The anyone who ever went skiing, running, “inflammasome” was undoubtedly the or hiking with him soon noticed. After a crowning achievement of Jürg’s career. This PhD in biophysics with Prof. Engel at the molecular machine consists of numerous Biocentre of the University of Basel, Jürg intracellular sensors, known collectively as moved to the Scripps Research Institute NLRPs (NACHT, LRR and PYD domains- as a postdoctoral fellow with Hans containing proteins) that, when activated, Mueller-Eberhard where he discovered associate with the adaptor protein ASC and that complement pores are formed by Caspase-1 to convert the interleukin-1β C9 multimers. precursor into a pro-infl ammatory cytokine. Copyright: F. Imhof © UNIL Nobody could have imagined the myriad This understanding of the complement 8 and therefore of death receptor-mediated of physiological and pathological triggers system led him to study other lytic apoptosis. He aptly demonstrated that c-FLIP of this pathway, including monosodium pathways upon his return to Switzerland did not only inhibit Fas-induced cell death, but urate crystals, asbestos and anthrax. This at the University of Lausanne. He could also activate non-apoptotic signalling elegant pathway suggested that autoimmune characterised cytoplasmic granules pathways, proposing that Caspase-8 might be manifestations in patients with genetic within cytolytic T cells (CTL) and involved in cell growth as well as cell death mutations of NLRP3 could be due to IL- discovered perforin, the major lytic processes; genetic studies confi rmed this 1β overproduction. Fortunately an IL-1β protein, as well as a family of proteases paradigm shift. He was also fi rst to implicate receptor antagonist (Anakinra) that had been known as granzymes. Jürg’s interest in the kinase RIP1 as an important player of sitting on the shelf for ~10 years could be studying the function of perforin in vivo the caspase-independent cell death program, tested immediately in these patients, resulting led to the generation of perforin-defi cient known today as necroptosis, and to provide in rapid and spectacular improvement of mice, which in 1995 still was a remarkable both a model and supportive evidence to their symptoms. This drug and other IL- endeavor. Analysis of these mice revealed unravel the long-standing molecular mystery 1βIL-1β receptor antagonists are now being a second lytic pathway employed by CTL, of how TNF-TNF-R1 signalling can induce used or tested in numerous infl ammatory that was dependent on the then recently either NF-κB activation (promoting cellular pathologies, ranging from gout to type 2 identifi ed death-inducing ligand, FasL, survival and activation) or cell death (the diabetes. To witness the translation of one’s and its receptor Fas (CD95, APO-1). so-called complex I and II model). research into effective medical therapy is This discovery turned Jürg’s interest the dream of all medical scientists, and to toward the TNF family of ligands with Using a bioinformatics approach, Jürg observe the rapid evolution of research on the corresponding family of receptors discovered several additional members of the “infl ammasome” into novel therapeutic (TNF-R family) and mechanisms of the TNF and TNF-R ligand and receptor strategies is perhaps the most appropriate apoptotic cell death. For these projects, families, including APRIL, BAFF and valediction of Jürg Tschopp’s legacy. Jürg combined his talent in the study of TRAIL receptors, respectively. BAFF is molecular mechanisms with his ever- now recognised as an essential survival and Jürg’s mind worked like that of a chess grand lasting keen interest in bioinformatics. differentiation factor for peripheral B cells master. He had a keen ability to recognise This began his most prodigious period and is being targeted in several ongoing patterns and possessed an uncanny instinct of research that included the discovery clinical trials for the treatment of certain for predicting molecular relationships. One of viral and mammalian forms of FLIP, autoimmune diseases. The numerous cell of Jürg’s trademarks was to reduce complex the physiological regulators of Caspase- death regulators identifi ed in Jürg’s laboratory questions to models so simple that they 20 ASI Inc. Newsletter June 2011 could only be right or wrong, and therefore young students and postdocs, to improve UPCOMING experimentally validated or discarded. He their work and possessed the rare attribute would joke that the half-life of models in his to be able to genuinely enjoy great scientifi c CONFERENCES laboratory was about two weeks. discoveries made by others, even his competitors. Therefore one of the highest 5th Vaccine & ISV Annual Global Jürg had several strong connections to plaudits for Jürg was that even his fi ercest Congress Australia and Australian Immunology. In competitors would all readily acknowledge October 2–4, 2011 particular he had a big infl uence on the careers that he was a “great bloke” and not just a Seattle, USA of John Silke, James Vince and Marthe great scientist. Perhaps a lesson from his www.vaccinecongress.com D’Ombrain (all currently working at WEHI), life should be that, particularly during the customerservice-vaccine11@elsevier. who worked for some time in his laboratory currently diffi cult times with funding, we com in Lausanne, and on Fabienne Mackay (Chair should enjoy each other’s scientifi c successes of Immunology, Alfred Hospital, Melbourne) more and be generous rather than trying to 5th Asian Congress on Autoimmunity who collaborated extensively with Jürg on stifl e our competitors, who in many ways (ACA 2011) the discovery of BAFF and April and their are also amongst our best friends. November 17–19, 2011 receptors. Fabienne recalls that Jürg was not Singapore just a wonderful mentor and an inspiration for In essence, Jürg Tschopp was a consummate Online abstract deadline: many years but also a person who truly cared scientist, a deep thinker on a broad array of Wednesday, June 1 about others and would go out of his way to issues, a great humanitarian and a highly Reduced registration rates end July 27 offer support and hospitality. Fabienne has civilized man, something that has always [email protected] been a regular visitor in Epalinges and the been distinguished by its rarity. I will www.kenes.com/autoimmunity privileged guest of Jürg’s laboratory retreat in remember him as a daredevil skier ever an isolated chalet with breathtaking views of ready to be challenged by a new double- 5th Congress of the Federation of the Alps where scientifi c presentations were black diamond or even better an off-piste Immunological Societies of Asia delivered in front of a roaring fi re, a place, run, an attribute that was clearly also evident Oceania (FIMSA 2012) –Translational which in itself spoke of Jürg’s personality in his science, always ready to tackle new Immunology in Health & Science – simplicity and greatness of nature. areas of research and diffi cult problems. The March 14–17, 2012 scientifi c community has lost a wonderful New Delhi, India Jürg generously supported many research mind. Jürg’s outstanding contributions, fi msa@fi msa2012.com projects on apoptosis, immunology and friendship, mentorship and collaborative www.fi msa2012.com infl ammation in Australia by providing spirit will be sorely missed. Our thoughts cytokines and antibodies, often before and condolences go to Jürg’s wife, Erna, V World Asthma & COPD Forum these reagents were commercially available his two children and wider family and his April 21–24, 2012 and even afterwards to allow cost savings. numerous present and past co-workers from New York, USA Moreover, Jürg was a frequent visitor and his wonderful laboratory in Lausanne. [email protected] intellectually highly generous contributor www.wipocis.org to conferences in Australia, also because his Andreas Strasser brother-in-law and family are Australians The Walter and Eliza Hall Institute of Medical 15th International Congress of Research Immunology living in Geelong. He loved coming to 1G Royal Parade Australia, particularly to interact with family Parkville Vic. 3050 Australia August 22–27, 2013 and friends. I (Andreas) will never forget that Phone: +61 3 9345 2555 Rome, Italy on one visit he not only agreed to transport Fax: + 61 3 9347 0852 [email protected] Email: [email protected] for our family a baby pram to Switzerland but www.ici2013.org delivered it to the door of my wife’s sister, Fabienne Mackay notably a 200 km drive from his home! Department of Immunology Faculty of Medicine, Nursing and Health Sciences Central Clinical School On a personal note, I (Andreas) am devastated Alfred Hospital as Jürg was my oldest friend in science. I fi rst Commercial Road The Walter and Eliza Hall met him at track and fi eld competitions in high Melbourne Vic. 3004 Australia school. Later, he was one of my instructors Phone: +61 3 9903 0712 Institute of Medical Research Fax: +61 3 9903 0731 at the Biocentre of the University of Basel, WEHI Seminars on the Web: Email: [email protected] teaching us undergraduate students column www.wehi.edu/seminars/ chromatography. At that time we also played together in the soccer team for our department at university.

Perhaps most endearing was Jürg’s collegial nature, his generosity not only with reagents but also of his creative mind. He was very willing to help other scientists, particularly

21 ASI Inc. Newsletter June 2011 ASI Councillors’ News Victorian News continue its current funding support and that The involvement of students in the DoI has funding levels will be at least maintained in become a priority for our local DoI organisers. the budget. As one example, this year 85 VCE secondary school students and teachers travelled A brighter story concerns the International from Melbourne, Bendigo and Ballarat After a hectic start to the year for the Day of Immunology held on April 29. There to participate in a full day Immunology many researchers who were preparing has been a lot of great work done by our program at the Gene Technology Access grants and fellowship applications, the local DoI committee to raise awareness of Centre (GTAC). This was so popular, a past month or two has been dominated Immunology through public and school repeat program was scheduled in May to by discussions about possible budget cuts activities associated with this day. Perhaps accommodate some of the many schools that to NHMRC medical research funding. partly as a result of the funding debate, missed out on the day. The organisers expect This possibility came as a bit of a shock media outlets were keen to help promote the even greater interest next year given the given the growing public and government day by interviewing local representatives, positive feedback received from the teachers support for medical research in recent such as Gus Nossal and Anne Kelso, about and students who took part in the day. The years. We have been fortunate that different issues in Immunology. The many annual DoI has taken on a life of its own in colleagues (especially at WEHI) initiated events on the day also included a featured Victoria and the committee organising the a very effective public campaign called article published in the Voice supplement DoI events is to be congratulated for raising ‘Discoveries need Dollars’ to highlight of The Age newspaper, discussions about the profi le of the day, and for increasing the public benefi ts of funding medical current issues in Immunology broadcast on public awareness and understanding of research. The campaign has involved local and national radio shows, an evening the importance of Immunology – and public rallies, email campaigns and public lecture delivered by Professors Liz immunologists! stories in newspapers and on television Hartland, Brendan Crabb and Anne Kelso and radio about the value of medical to a very receptive audience of 130 people Stuart Berzins research and the potential damage to (an extremely good turnout on a Royal Councillor the sector that could result from budget Wedding night!), and a variety of educational cuts. At the time of writing, there is activities involving primary and secondary some optimism that the government will school students.

22 ASI Inc. Newsletter June 2011

N.Z. News NZ ASI/Immunet Meeting 2011 Registration has closed for the upcoming NZ ASI branch meeting to be held at the new Alan MacDiarmid building, Victoria University of Wellington from June 30 to July 1. Our keynote speakers will include Paola Castagnoli (Singapore Immunology Network, Singapore), Kiyoshi Takeda (Osaka Graham Le Gros, Joanna University, Japan), and Ranjeny Thomas Kirman, Anne La Flamme, (University of Queensland, Australia). We are presenters at DoI 2011 expecting another exciting meeting with well over 100 of our members participating.

Day of Immunology Celebrations Wellington This year, because the Day of Immunology was on the same day as the Royal Wedding, we decided to hold two separate events in Wellington. First, we had a series of short public lectures to celebrate the Jo Kirman giving lecture Royal Wedding entitled “A Marriage of at DoI 2011 public Convenience: Partnering with Microbes for lecture Better Health.” These lectures took place at Victoria University of Wellington and were followed by a “wedding” reception. The second event was a quiz night on May 5 called “Plagues and Pestilence”. With this event we endeavored to nourish the public with immunology in the guise of pizza and crisps. Both events were hugely successful and were fi lled to capacity. Anne La Flamme giving lecture at DoI 2011 Dunedin Roslyn Kemp and Alex McLellan organized the celebrations in Dunedin. On April 28 there was a public lecture by Dr Nikki Turner, Director of the Immunisation Advisory Centre, on “Vaccination: Not Just a Shot in the Dark”. The lecture was held at 5pm in Hutton Lecture Theatre, Otago Museum, Dunedin and was preceded by refreshments and lively debate.

Anne LaFlamme Councillor

DoI quiz night

Dr Joanna Kirman (left) & Dr Anne LaFlamme at DoI quiz night

23 ASI Inc. Newsletter June 2011

S.A./N.T. News continuing exciting addition to this year’s Brice, Anastasia Yu, Kate Parham, Kiwi meeting. Our student reps Kiwi Sun and Kate Sun, Susan Christo, Siti Noordin and Sally This year is an exciting time to be in Parham have helped to organize the student Sun. An advertisement of the exact date and Adelaide as an immunologist. We are functions and have set up a Facebook page for call for abstracts will be sent out by email gearing up to host the 41st ASI Annual the meeting. For all those social networkers to all SA/NT ASI members in June. Please Meeting to be held at the Adelaide out there, please visit the page and keep up support this event if you are a supervisor Convention Centre, 11-15 December to date on what’s happening. The Facebook by encouraging your students and staff to (2011). The organizing committee has link is: https://www.facebook.com/group. attend as it is a great opportunity for them been working hard to ensure that our php?gid=131570183544771. I would like to give an oral presentation to their peers in meeting will be a success. We have to thank all of the committee members for a relaxed environment. Another incentive secured top international speakers (Lisa their continuing efforts in the planning of ASI is that there will be three prizes conferred Coussens, Richard Flavell, Michael Adelaide 2011, especially our Convenor, Dr for the Best Presentations given by a PhD Karin, Paul Kubes, Alberto Mantovani, Claudine Bonder who is working tirelessly Student, Honours Student and Research Claudia Mauri, Michel Nussenzweig, Ed to ensure smooth sailing toward a terrifi c Assistant (one in each category). We are Palmer, Shugeru Saito, Joachim Schultze conference event. looking forward to another great AIR event and Megan Sykes) and the planning for this year. For queries or more information, the Tumour Immunology (co-ordinator: On another note: we have just formed the I can be contacted by email at michele. Dr Cara Fraser), Infection and Immunity committee for the 7th Adelaide Immunology [email protected]. We look (co-ordinator: Dr Erin Lousberg), Retreat (AIR) for PhD students, Honours forward to seeing you there! Transplantation (co-ordinator: Prof students and research assistants to be held in Toby Coates) and Prograd (co-ordinator: late August this year. Our AIR7 committee Michele Grimbaldeston Dr Lindsay Dent) workshops are well members are Cara Fraser, Erin Lousberg, Councillor underway and they promise to be a Iain Comerfold, Lachlan Moldenhauer, Sarah

24 ASI Inc. Newsletter June 2011 Poster Prize Winner Bernice Tan, Garvan Institute, Sydney

I was fortunate enough to have the interesting gene because it has been shown patterns to BIRC3 mRNA expression opportunity to participate and to present to be associated with the TNF signaling kinetics in mouse islets and MIN6 cells, my work at ASI annual meeting in Perth pathway and also play a role in regulating indicating the BIRC3 promoter region in the form of a poster. It was an enriching apoptosis in other cell types. contains cytokine responsive elements. experience being presented with high quality Subsequent work also showed that talks and posters. My PhD project aims to understand the role blocking of NF-κB activation suppressed of BIRC proteins in pancreatic beta cells BIRC3 expression, demonstrating that I am a third year PhD student working and understand the signaling processes in NF-κB is a major regulator of BIRC3 under the supervision of A/Prof. Shane pancreatic beta cells under infl ammatory transcription. In addition, we found Grey at the Garvan Institute, Sydney. Our stress with cytokines such as TNFα. So far, over-expression of BIRC3 in MIN6 cells laboratory focuses on Type 1 diabetes and we found differential basal mRNA expression was suffi cient to induce activation of an transplantation. Type 1 diabetes is a disease of BIRC family genes in isolated primary NF-κB reporter, and NF-κB activation where pancreatic islets are infi ltrated with BALB/c islets and MIN6 pancreatic beta was further potentiated in the presence immune cells, which attack and destroy cells. Interestingly, under conditions of of TNFα. With the view that BIRC3 is insulin producing pancreatic beta cells infl ammation, BIRC3 was induced in MIN6 important for TNFα-mediated NF-κB leading to a loss of glucose regulation. cells, primary mouse islets and human islets, signaling in islet cells, we accessed One of the mechanisms that cause beta cell following stimulation with TNFα. We then NF-κB signaling in BIRC3 knockout destruction is the secretion of infl ammatory went on to examine how BIRC3 is regulated islets. Surprisingly, BIRC3 knockout cytokines by the immune infi ltrate. Cytokines in pancreatic beta cells. We found blockade of islets showed normal NF-κB activation such as tumour necrosis factor alpha (TNFα) gene transcription in vitro with actinomycin by western blot and TNFα-induced contribute to the pathogenesis of type 1 D, suppressed BIRC3 expression, suggesting expression of A20, a canonical NF-κB diabetes by impairing pancreatic beta cell that BIRC3 is regulated at the level of regulated gene, compared to islets from function and causing beta cell apoptosis. transcription. Analysis of the proximal WT littermates. However, BIRC3-/- islets However, the molecular processes that are promoter region revealed a region rich in showed reduced expression CCL2 and induced in pancreatic beta cells by TNFα putative transcription factor binding sites CXCL10 expression with TNFα. There are not well understood. In order to better for NF-κB, STAT, p53 and AP-1. This is are evidences showing that CCL2 and understand the effects of TNFα on pancreatic interesting because cytokines such as TNFα, CXCL10 genes are co-regulated by not beta cells, our group used a microarray IL-1β and IFNγ are known to signal through only NF-κB but also by p38 and JNK. approach to identify early immediate transcription factors that bind these sites. In We propose that although BIRC3 alone response genes expressed in mouse islets order to further study the BIRC3 promoter may be suffi cient for activating NF- following TNFα stimulation. From the activity with cytokines, this region of the κB, in the presence of TNFα, BIRC3 microarray, we saw BIRC3 but not the other promoter was cloned and placed upstream of may be providing a positive feedback BIRC family members are regulated in mouse a luciferase reporter. MIN6 cells transfected mechanism on NF-κB signaling. In the islets in the presence of TNFα. BIRC3 is an with the BIRC3-reporter and stimulated absence of BIRC3, islet cells may still with TNFα displayed identical induction have normal NF-κB signaling. We are now working on the hypothesis that in pancreatic beta cells, BIRC3 may play a role in regulating other TNF- induced signaling pathways such as p38 MAPK, and JNK.

Lastly, I would like to take the opportunity to thank my supervisor for his mentorship throughout the course of my PhD. This award would not be possible without him. The award came as a pleasant surprise despite my abstract falling in the miscellaneous category. The prize was defi nitely a pat in the back and a form of recognition to my work. Thank you ASI and the generous sponsors! Members of the Lab 54 lab: (LtoR) Stacey Walters, Figure 1 Dr Eliana Marino, A/Prof. Shane Grey, A diagram showing the hypothetical TNF Jeanette Villanueva, Elisabeth Malle, signaling pathways in pancreatic beta cells Nathan Zammit and Bernice Tan

25 ASI Inc. Newsletter June 2011 International Day of Immunology 2011, Melbourne Angela Chan and Claerwen Jones, University of Melbourne

On Friday 29th April, secondary students Prof. Andrew Lew and Prof. Peter Doherty In the evening, a public lecture series and their teachers, the media and members treated students to a rousing introduction was held at the University of Melbourne. of the public joined with immunologists to Immunology. A range of activities in the Dr Irina Caminschi (WEHI) chaired the to participate in a series of activities lab gave the students a strong foundation evening and gave a great introductory talk around the theme “Your Body At in Immunology in preparation for the setting the stage for the war between men War!” to celebrate International Day of Immunology component of their Biology and microbes! Prof. Elizabeth Hartland Immunology in Melbourne. course. This included the “Your Body at (Dept of Microbiology and Immunology, War” exhibition – a stunning collection The University of Melbourne) followed, There was great media interest in the of informative posters about the immune discussing how bacterial pathogens lead up to the International Day of system; “Putting Immunology under the disarm inflammatory responses by Immunology. The Committee worked microscope” – a microscopy workshop where blocking innate signalling pathways in with journalists to prepare a front-page students looked at immune cell involvement an interesting talk entitled “Bacterial article in the Voice supplement of The Age in infection, cancer and autoimmune disease; diarrhoea: infection by stealth”. Prof. discussing immunisation rates, following and “Bonding with your antigens” – where Brendan Crabb (Burnet Institute), in the retraction of Andrew Wakefi eld’s students performed an ELISA to learn his thought-provoking talk “Fighting paper linking vaccination with autism. about antibodies and their applications. The malaria; and the evolution of humans”, The article featured expert commentary students then listened to inspiring career spoke about the coexistence of the by Sir Gustav Nossal, Laureate Prof. talks by PhD student Dimitra Zotos (WEHI), malaria parasite and homo sapiens over Peter Doherty and Prof. Anne Kelso Industry scientist Brent McKenzie (CSL) the last 200,000 to 400,000 years and was followed by broadcasts on local and award-winning biomedical animator and the evolutionary selective forces and national radio, including Einstein A Drew Berry (WEHI). Feedback comments wrought upon the human genome by this Go-Go on 3RRR (Anne Kelso, 17/4/11), from students and teachers included: “It disease. Finally, Prof. Anne Kelso (WHO the Adam Spencer Breakfast Show on was excellent. Everything about the day Collaborating Centre for Reference and ABC 702 radio (Gustav Nossal, 29/4/11), was wonderful”; “Great variety of tasks Research on Infl uenza) gave an excellent and ABC News Radio (Anne Kelso, and amazing selection of speakers”; “Very talk on “The continuing challenge of 29/4/11). interesting and engaging. Helped me infl uenza” describing the 2009 H1N1 consider a path in medicine”. The day was infl uenza pandemic and explaining the A full day Immunology program was held such an overwhelming success that a second role of the World Health Organisation’s at the Gene Technology Access Centre Immunology program was run at GTAC for Global Infl uenza Surveillance Network (GTAC) for 90 VCE Biology (Year 12) students from another nine schools on Friday in monitoring future pandemic viruses. students from nine schools. Students 20th May, with Prof. Phil Hodgkin and Sir A very receptive audience of 130 people travelled from Melbourne, Geelong and Gustav Nossal giving the opening address. attended the evening seminar, which Ballarat to participate in the day. Assoc. was a great turnout for a Friday night that coincided with the Royal Wedding! Light refreshments followed the talks, allowing audience members a further chance to chat with the lecturers. The talks can be heard on the following weblink: http://harangue.lecture. unimelb.edu.au/Lectopia/Lectopia. lasso?ut=1448&id=113511#

Although April 29th has now come and gone, International Day of Immunology events are still not over! The Committee is running a competition for primary school students, which closes on Friday 1st July. This competition encourages primary school children to think about what happens when they get sick with a virus, and depict the battle between the body’s immune cells and the invading virus as a collage (grades 1-3), or as a short video or digital story (grades 4- VCE Biology students “Putting Immunology under the microscope” at GTAC 6). Winning entries will receive some (Photo: Katrina Ferguson, Monash University) incredible prizes for the students and

26 ASI Inc. Newsletter June 2011 their classroom. ASI members are asked science communication. Participation in the communication and media relations, to promote this competition to their local committee provides a wonderful opportunity sourcing event sponsorship, and working primary schools. Participating schools will to network with fellow immunologists from as part of a dynamic “bring science to be sent out information packs to inspire and across Melbourne research institutes and the public” committee! Interested people educate! Further details can be found at the universities and provides an opportunity should contact Claerwen Jones at cmj@ following weblink: http://www.immunology. to get experience in event organizing, unimelb.edu.au. org.au/wdi.html

This year’s Day of Immunology has been an outstanding success thanks to the generous support of our speakers and our sponsors and the tireless efforts of committee members and GTAC staff, particularly Tony Chiovitti and Brian Stevenson. The Committee would like to gratefully acknowledge the support from the following organizations: Australasian Society for Immunology, Immunology Group of Victoria, Walter and Eliza Hall Institute of Medical Research, The University of Melbourne, Burnet Institute, Peter MacCallum Cancer Centre, Monash University, GTAC, Bio-Rad, CSL, BD, Life Technologies, Interpath Services, SPP Medical and Legal Books, Australian Geographic, Offi ceworks.

The Day of Immunology committee is looking “Bonding with your antigens”: for new members for 2012 as we continue to Jess Reiseger assisting VCE Biology students perform an ELISA at GTAC”. showcase Victoria’s contribution to medical (Photo: Katrina Ferguson, Monash University) research and encourage new initiatives in

Discoveries Need Dollars rally, Brisbane, 19th April 2011

Above: Andreas Suhrbier and Michael Good

Right: The rally in Brisbane

(Photos: Mimi Kersting, QIMR)

27 ASI Inc. Newsletter June 2011 Queensland Day of Immunology 2011 Merja Ruutu, Diamantina Institute

It all started overseas. Weird things I had strong support from Chris and Alejandro he was thinking of us if we didn’t get our happen in conferences: people meet each Lopez and money from ASI with the help of vaccinations. Assoc. Prof. Maher Gandhi other, start talking over the drinks, one State Councilor, Ash Haque. With a few really from QIMR revealed how dangerous kissing thing leads to another … That is how I awesome volunteers, we made it happen. can be and how miracles do happen through realized Queensland doesn’t celebrate the immunologists’ hands. Dr Andrew Cotterill Day of Immunology, after bumping into Our DoI was held at PA Hospital on 27th and Prof. Ranjeny Thomas talked about Chris Schmidt in Japan. And I decided April. We had an immunology quiz created diabetes and arthritis and what happens when that something needs to be done to that by students and RAs; we had a corner where the immune system goes haywire and starts shameful fact. you were able to dress as an immunologist a civil war in our body. All talks were really and have photos taken. Dr Sandrine Roy interesting and gave us both information and However, soon I realized that it is brought a brightfield microscope and entertainment. quite hard to introduce new things into interesting slides with her and we were able people’s minds, and raising interest for to see, at a microscopic level, the havoc that It was quite a challenge to organize the DoI; the concept of the Day of Immunology diabetes does to your pancreas and arthritis however, the fi rst time is always the hardest. was challenging. But in Finland we to your joints. It may not be perfect no matter how you plan have a thing called ‘sisu’. That could be it. But you have to start somewhere and, translated to ‘bloody hard will’. With We had great lay talks in different areas of with practice, you will succeed. One day. that we pushed Russians from our border immunological research. Professor Andreas Stay tuned for that. during WWII and made Nokia one of the Suhrbier from QIMR started by telling us leading companies in the mobile phone hard facts about vaccination. His colourful business; and with ‘sisu’ I would make presentation made us shake with laughter. Day of Immunology happen. In the end, we had no doubt as to what

Professor Andreas Suhrbier giving his vaccination talk

Dr Merja Ruutu

28 ASI Inc. Newsletter June 2011 ASI STUDENT NEWS Contributions sought The past few months have been an uneasy for Immunology meeting in Adelaide. With for the ASI online time for scientists with the threat of only six months until the festivities begin, cuts to medical research funding in the organisation of the student function is well immunology quiz May budget! In response, the scientifi c underway, with the venue chosen as the community has rallied with a number of Adelaide Rowing Club, and our focus now As part of World Day of grassroots campaigns launched, notably the turned to entertainment! Immunology events, we have Discoveries Need Dollars initiative (www. developed an online discoveriesneeddollars.org) which has Just to remind people that there is ASI Student immunology quiz (see http://www. organised rallies in a number of capital cities. Facebook which all members are welcome immunology.org.au/immquiz1. Hoards of scientists (including ourselves!) to join. We want to maximise the use of it html) took to the streets and steps of Parliament for better networking amongst us, so we will on the ASI website. This quiz is House (in Adelaide) to make our voices set up some Facebook discussions based targeted at the general public, but heard! I hope many of our fellow ASI student on different research areas (e.g. B cells, T it would be good to add a few members took the opportunity to fi ght for cells, DCs). Members are encouraged to more questions (especially some our future, as any cuts to medical research introduce themselves and participate in with an Australian fl avour), and funding will impact early career researchers discussions covering a number of topics maybe even add an “Advanced greatly! Hopefully, by the time this goes to including research areas, the social function, Level”, with questions that press, anxiousness will have eased, with the collaboration opportunities and destinations undergrad students might fi nd government listening to our pleas and making for post-doc studies. Any discussion topics useful for revising for exams. the right decision (fi ngers crossed!). which are not available can also be set up by All that’s needed now are the request. Please feel free to contact us! questions and answers. On a lighter note, we are now half way through 2011 and, as PhD students, the Kate Parham and Kiwi Sun If you would like to contribute speed at which this year is passing is not ASI Student Representatives 2011 any multiple choice questions appreciated. After a 5-day Easter/ANZAC for either the general quiz or an day long weekend (or a mini holiday) it advanced version, please send is a great opportunity to return to the lab them to Judith Greer at refreshed and ready to knuckle down and [email protected]. produce some amazing data to share with our peers at the 41st Australasian Society

Rally at Parliament House, Adelaide

29 ASI Inc. Newsletter June 2011 Travel Award Conference Reports 14th International Congress of Immunology Kobe, Japan, 22–27 August 2010 Zheng Lung Ling University of Sydney

I was extremely fortunate to be awarded development/differentiation of immune my project is currently revolving around the ASI International Travel Grant to cells, lymphocyte regulation, and clinical cell-derived microvesicles, I managed to allow me to attend the 14th International immunology, with each category further fi nd, among many other interesting ones, Congress of Immunology in Kobe, Japan. divided into even more sub-categories. a poster by Lisa Ayers from Oxford, UK, Words could not describe how excited Deciding which talks to attend was very about methodologies used in microvesicle I was about the prospect of attending diffi cult. I was particularly drawn to the detection; and Tamer Kahraman from my fi rst major international conference lunchtime lectures (partly for the free lunch Turkey whose poster was about increased of this magnitude, and also Japan had for those with shallow pockets) which microvesicles levels in Behcet’s Syndrome always been a destination that I dreamt of were presented by some of the renowned and asthma patients. It was suggested that visiting. Furthermore, I had the privilege immunologists, such as Professor Foo-Yew I could use a novel label for microvesicle of going with my supervisor, Professor Liew from University of Glasgow, who spoke detection, and Lisa was particularly Nick King, and two of my fellow PhD of the role of IL-33 and IL-35 in infection interested in how I processed my electron students from the lab, Amanda Yeung and autoimmune diseases, where IL-33 has microscope specimens. and Rachael Terry. a pro-infl ammatory property in infection and infl ammation, and can induce a Th1 to Th2 Also during the conference I was deeply Upon arriving in Kobe in the evening, our response shift. Another interesting lunchtime impressed by the courage of some of the fi rst impression was how humid, hazy, and lecture was delivered by Professor Shimon young Japanese scientists to deliver oral warm Japan was at the time of the year. Sakaguchi on a broad review on regulatory T presentations despite the fact that English Although having grown up in a tropical cells in tolerance and immune homeostasis. was far from a familiar language to them. It country like Malaysia before moving The lecture included the origin of regulatory was amazing how some went to the extent to Australia and accustomed to the hot T cells, their mechanisms for immune of memorising every syllable and gave a full and humid climate, I was overwhelmed regulation, and also various approaches and 20 minute presentation. This is something by how sticky and unpleasant it was! parameters in immune therapy and their that I will never be able to do in front of an By the time we made our way to our success. audience. hotel, we were sweating like we had just been to a sauna. However, a couple Other than the plenary talks and lunchtime By the end of the conference, I had more of days later, the haze in the form of lectures, the conference was packed with or less fulfi lled my objectives of attending water vapour dissipated; but the heat numerous symposia of excellent quality. this conference which were, firstly, to from direct sunlight was immense Of interest was the talk by Professor Adrian present my novel research and exchange throughout our trip. Perhaps we should Hayday about oligo-clonal lymphocytes, ideas and opinions; secondly, to broaden not be complaining, as that could be the which respond to stress antigens and enhance my perspectives by attending various reason why the airfare was relatively Th2 responses. The talk also discussed novel presentations that were not directly related cheap at the time. communication pathways between epithelial to my project; and thirdly, to explore future cells and resident lymphocytes in the skin career possibilities around the globe. At the registration desk, we were hit by and gut. There was also a talk by Professor Overall the event organisers did a fantastic the fact that The International Congress Shigekazu Nagata about the clearance of job organising and managing an event of of Immunology was indeed in a different apoptotic cells by phagocytes, league to the average conference we and failure to clear apoptotic had been attending in the past when we cells or properly degrade their were overwhelmed by the sheer volume cellular components could result of abstracts in the form of several in severe autoimmune diseases kilograms worth of books and thousands such as severe anaemia and of attendees fl ooding the Convention chronic arthritis. Centre. As a result, we were in a dilemma of whether to spend the evening strolling The poster sessions featured the streets of Kobe, or to go through the walls and walls of countless abstracts so that we could decide which posters each day throughout the sessions to attend the next day. Tough! duration of the conference. There were simply too many of them The conference itself was packed with to go through with reasonable quality contents from all aspects of detail, and one could only scan immunology, including infection and the titles and hope to be captured immunity, tolerance/autoimmunity, by keywords of interest. As 30 ASI Inc. Newsletter June 2011 this magnitude and made sure that it ran Keystone Symposium – Immunologic Memory, smoothly. Persisting Microbes and Chronic Disease When the conference concluded, we could Banff, Alberta, Canada, February 6–11, 2011 not resist the temptation of staying back a Sarah Moneer few days to visit the attractions that Tourism University of Melbourne Japan had to offer, despite the fact that we all had so much to do back in the laboratory at Earlier this year, I had the privilege to the presentations without being forced home. It is no wonder that Japan has always attend the Immunologic Memory, Persisting to choose. The program also allowed been one of the top holiday destinations for Microbes and Chronic Disease Keystone ample recreation time for conference tourists around the world. The castles that we symposium in the picturesque town of attendees to explore the many wintery managed to visit and the countless temples, Banff. wonders of Banff. gardens, and parks were simply amazing. We travelled along the south coast by the My journey began with a 22-hour fl ight to The fi rst session of the conference was famous Japanese bullet trains, and had the Calgary, followed by a 1½ hour bus ride opened by the University of Melbourne’s opportunity to visit the Hiroshima Castle from Calgary to Banff. After checking in at own Professor Frank Carbone, who (although it was a rebuild), Himeji Castle the front desk (surprisingly, with an Aussie spoke about his group’s research into (original! But under restoration), Osaka receptionist), I had barely enough time to anti-viral T cell memory and protection Castle (another rebuid), and what was left dump my luggage in my room, change into in non-lymphoid tissues. True to its name, of the Imperial Palace Garden in Tokyo. We some fresh clothes and dash to the conference the symposium had a strong focus on also managed to squeeze Nara, Kobe, and centre before the beginning of the Welcome memory T cell subsets, differentiation Kawaguchi-ko Lake near Mt Fuji into our and Keynote Address. I’ll be honest – after and transcriptional regulation in a agenda in the extremely short period of time being awake for over 24 hours, crossing setting of chronic infection. The talks that we had left, but the scenery was simply two continents and shifting from Australian were both enlightening and incredibly stunning, even though it was off-season, summer to Canadian winter, much of that educational. John Wherry and David which means there was no snow on the opening keynote speech was a blur. Future Brooks introduced me to the role peak of the mountain and it was covered by ITA winners please note: when travelling to of T-bet and Bimp-1 in memory T clouds most of the time. One could only stare a conference on the other side of the world, cell differentiation; Rafick Séckaly at postcards and imagine what the scenery it is advisable to arrive the night before. impressed upon me the role of PD1 in would look like in fl esh. regulating T cell activity; and Bob Seder Following a good night’s sleep, my conference stressed the importance of examining Walking along the vibrant and colourful experience improved signifi cantly. Being polyfunctionality when determining the streets really immersed us into the modern such a specialised meeting, the conference quality of a T cell response. B cells were culture of Japan. There were endless was much smaller and the program more not to be neglected, however, with Andrea attractive restaurants, confectionaries, and relaxed than the hustle and bustle I had Cerutti, Falk Nimmerjahn and Susan Moir street foods tempting us to try as much as grown accustomed to at the annual ASI giving fascinating presentations about our stomach and pockets allowed. There was meetings. There were no concurrent sessions the regulation and quality of antibody just so much to see and experience! As you running, so one was able to attend all of responses in infection. would imagine, we did not have the time to immerse ourselves in what Japan had to offer, rather, we had a quick glance at what Japan was like, and we were EXHAUSTED and hot tempered towards the end of our trip from the heat and rushing around and also minimal hours of sleep; but overall it was an awesome experience. We were already missing Japan by the time we were on our way to the airport.

I would like to sincerely thank ASI for providing me the opportunity to witness and be part of such a major event at the ICI conference. Without the support of the travel grant from ASI I would never have the opportunity for such an amazing experience at this stage of my life. Sunrise over the Rockies 31 ASI Inc. Newsletter June 2011

A special mention must be made for Dr Keystone Symposium – Rafi Ahmed, an incredibly prominent T cell biologist at the Emory University Stem Cells, Cancer & Metastasis Meeting School of Medicine in the United States Colorado, USA, March 6-11, 2011 and deliverer of the fi nal Keynote speech. Edwin Hawkins I lost count of the number of presenters Peter MacCallum Cancer Centre, Melbourne who acknowledged Rafi and his group in There is always that point when buried deep separate patients were transplanted into their presentations. Rafi ’s talk was, in fact, in the bowels of Los Angeles International large cohorts of recipient mice. Once these my favourite of the entire conference. He Airport immigration, after a 15 hour fl ight cohorts presented with tumours, single demonstrated that antibodies generated wedged between a few people who really cells were again isolated and transplanted to the conserved stem of hemagglutinin should have bought an extra seat, you still into subsequent large cohorts of mice. (versus the polymorphic globular head) need binoculars to see the front of the queue Microarrays were then performed on the could bind all H1 variants and limit and less than 45 minutes to your connecting tumours at every stage to determine whether infection, thereby potentially overcoming fl ight, you stop and think to yourself, “Is the molecular signature was maintained due the issue of antigenic drift and variations this really all going to be worth it?” But to a single cancer stem cell or if divergent between different seasonal fl u strains in quickly after arriving at the Keystone resort populations were produced. The size of vaccine design. in Colorado, USA, it all seemed worthwhile. the studies and the experimental design I found this Keystone conference to be of this work was truly staggering and had The conference was not all work and no something quite special, and I encourage a signifi cant impact on how I now think play. During our various recreational those students and post-docs who have yet about the function of cancer stem cells. breaks I had the chance to explore to attend one to do so. Previously, I have Furthermore, the commitment to presenting the town, go cross-country skiing on attended large international conferences and large portions of unpublished data was a breathtaking trail near the hotel (or become consumed by the sheer numbers extremely refreshing. castle, rather – it was HUGE) and walk of other attendees which makes movement along the icy trail by frozen waterfalls in between sessions impossible and access to The other highlight of the meeting was the Johnston Canyon. Being surrounded by any of the invited speakers non-existent. snow. The organisers leave a 6-hour break the Canadian Rockies and endless rows from 11am to 5pm every day to brave the of pine trees draped in blankets of snow But this conference was an exception. A slopes. This, combined with the fact Keystone was truly a memorable experience. commitment from organisers to keep delegate has had its best season in 10 years, 13km2 numbers small in combination with truly of ski-able terrain, 135 runs (some as long So, thank you ASI for granting me this spectacular locations means you would as 6km), meant I was more than prepared international travel award and enabling struggle to fi nd a better way to spend six to gamble the health of my body against me to attend this spectacular conference. days. This was considered a large Keystone the cost of America’s hospital system I would highly recommend attending this meeting with just over 400 delegates, in order to have a good time. And to be meeting to all T cell enthusiasts who don’t however the feeling of the meeting was honest, it was worth every potential $10,000 mind a little cold. still very intimate and the effort by senior denomination of damage. Although you delegates to attend and interact at poster might have received a different answer from sessions was excellent. The theme of this the group of delegates on crutches and casts Keystone meeting was Stem cells, Cancer and that accumulated at the rear of the seminar Metastasis and was nestled at the Keystone room as the conference progressed. But, that resort about two hours out of Colorado. Being feeling of catching a snowcat to 12,000 feet an immunologist who now masquerades as (see photo) and snowboarding on untouched a cancer biologist, it is nice to realise that snow was something extremely special that the key questions that underpin the biology I will never forget, even if I did almost kill of both problems remain the same. That is, another delegate from the Garvan Institute understanding and appreciating how cells by attempting to snowboard underneath a grow, die and differentiate enables you to tree, bumping it slightly and subsequently “wing it” about 90% of the time when talking off topic.

The scientifi c highlight of the meeting for me were Sarah in snowy Banff the herculean efforts of Sean Morrison to dissect out the true “stemness” of cells that allow cancer cells to regenerate tumours. Professor Morrison presented a massive study where single human melanoma cells from 32 ASI Inc. Newsletter June 2011

before my trip and was this roughly translates to 2.16 metres of subsequently accused of snow, but there was defi nitely something trying to purchase my beer cooler about saying 1 Shaq. Boston is an with counterfeit money. extremely comfortable city and not too Now, from my extensive dissimilar from Australian centres such knowledge of action as Melbourne. There is a defi nite smell of fi lms (although from my academia in the air with Harvard, MIT, recollection the fi lm Boyz Massachusetts General Hospital and all ‘n’ The Hood was not set in their subsidiaries scattered around the a ski resort), I knew there city. The take home message for anyone was a very high chance considering visiting Boston for a post that my friend behind the doctoral placement is that if you can initiating a mini two-metre avalanche in counter was surely packing a wide array of deal with the Shaq related units of snow his path. Oh well, with the pressure on the fi rearms, so I declined to argue with him. each year, the access to technology and NHMRC to cut the budget, it would have Instead, I left the store, emptied my wallet into potential to collaborate with some of the just meant one less grant to fund (Sorry the nearest muddy pile of snow, jumped up best labs in the world is quite special. Simon!). and down on the contents for a minute or two and returned a few hours later. Success. In summary, it really was a fantastic trip The lowlight of the conference was walking and I felt extremely privileged (usually 50 metres at 9,400 feet of altitude in the After six great days at Keystone, it was back when pimping it out in Keystone) to Keystone village. Yes, as a prelude to to the real world and time to prepare for visits receive the opportunity to take such a trip. old age and retirement villages, even the to labs in Boston and London. Upon arrival in In reality, without the continued fi nancial simplest of tasks at high altitude seems Boston I was quickly informed what a terrible support of ASI, trips like this would diffi cult. The small walk to pick up beer and winter they were having this year. In fact, be far more diffi cult for post-docs. So groceries on the fi rst day ended up feeling they had resorted to measuring the amount thank you to the ASI for the opportunity like the entire journey from all three Lord of snow they had received that year in units to attend a great conference and have a of the Rings movies jammed into one 10 of the basketball player Shaquille O’Neal. fantastic post-doc tour. I encourage all minute blockbuster. The adventure of this For example, in conversation multiple times ASI members who are eligible to apply trip was then rounded off when I pulled out I heard: “Yeah, we’ve had 1 Shaq worth of for the next round of funding and wish you my crispy US dollars acquired in Australia snow this year” in a thick Boston accent. Now, all good luck with your applications!

SPF MICE AND RATS CUSTOMISED BREEDING MAINTENANCE OF STRAINS IMPORT AND EXPORT CRYOPRESERVATION

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33 ASI Inc. Newsletter June 2011

40th Keystone Symposium – Immunoregulatory Networks Breckenridge, USA , April 2011 Eric Tu Department of Biochemistry & Molecular Biology, University of Melbourne

I was fortunate to receive an ASI are fully functional and have been A poster session of 2½ hours was set up International Travel Award which gave shown to be essential in suppressing each day after dinner and around 50 posters me the opportunity to attend Keystone infl ammation triggered by obesity, were presented at each session. Last year I Symposia: Immunoregulatory Networks, which is linked to the development of attended the 14th International Congress of and visit some of the most renowned insulin resistance. Immunology in Japan and I was overwhelmed labs in the fi eld of immunology. The • Dario Vignali’s (St Jude Children’s by hundreds of posters presented in the conference was held from 1-6 April at Research Hospital) presentation of his poster session daily. In comparison, I much Beaver Run Resort, a major ski resort results on a new Treg population that preferred the session at Keystone since I was in Colorado, USA, attracting around produces the inhibitory cytokine, IL- able to interact more with other scientists 400 attendees. There were morning and 35. He showed that treatment with IL- and was able to seek out the posters that night sessions each day and the interval 35 induced a regulatory population in I was highly interested in. I presented a between 11:30am to 5pm was especially both naïve human and murine T cells. poster on a portion of my PhD project titled: reserved for attendees to ski and enjoy These IL-35-induced Tregs display “TGFβ-induced autoantigen-specifi c Foxp3+ facilities at the resort. However, just like comparable or improved suppressive regulatory T cells promote regeneration many other attendees, I suffered from capacity over natural Tregs and mediate of tissue in fully-established autoimmune suppression via IL-35, but not TGFβ or serious high altitude sickness during diseases”. During the poster presentation, I IL-10. Most importantly, IL-35-induced was given valuable exposure and feedback the entire conference and missed out on Tregs neither express nor require Foxp3 the opportunity to ski at such a fantastic for their regulatory functions. which greatly aided in the formulation of place, which was really a pity. ideas for my thesis and design of future • Wanjun Chen’s (NIH) talk that experiments. I was pleasantly surprised by The conference was a regulatory T cells TGFβ is not only required for the the number of people who were interested (Tregs)-centric meeting, and focused generation of induced Tregs in the in my area of research. I was also given on how regulatory T cells interact with periphery and natural Tregs in the the opportunity to speak with some other other cell populations and utilise different thymus, but is also required for the researchers about their fantastic work. + + cytokines to prevent autoimmune development of TCRαβ CD8αα intestinal intraepithelial lymphocytes diseases and regulate immune responses. Prior to the conference, I travelled to (IELs). Strikingly, his group has High-quality speeches were given at discovered that TGFβ can also induce Washington DC where I visited Ethan this conference by many well-known the re-expression of repressed CD8α in Shevach at NIH, who is no doubt one of immunologists, no doubt attracting a lineage-committed peripheral CD4 T+ the most respected researchers in the Treg lot of talented post docs and students. cells. fi eld. There I presented an hour-long talk to Vigorous discussions always ensued his lab members and received many good after each talk which demonstrated the • Following Wanjun Chen’s talk, Hilde suggestions on advancing my work. I was novelty and signifi cance of science being Cheroutre (La Jolla Institute for Allergy extremely grateful for Dr Shevach and his presented in this meeting. Some great & Immunology) presented work from lab members’ hospitality. Whilst at NIH, I talks of the meeting for me included: his lab which demonstrated that a new also had the chance to visit Kristin Tarbell regulatory population, CD8α+CD4+ and Wanjun Chen to talk about potential IELs, were converted from CD4+ T • Diane Mathis’s (Harvard University) cells in a TGFβ-dependent process. post doc projects and showcase my work to keynote address on the role of Tregs CD8α+CD4+ IELs express regulatory their lab members. I was really amazed by in tissues. A high percentage of and also cytotoxic phenotypes. the depth of knowledge and comprehension Tregs (60% of CD4 T cells) is found Moreover, the presence of CD8α+CD4+ of people in NIH. Although most of them in adipose tissue and these Tregs IELs correlates with less or no disease worked on something totally different to have distinctive gene profi les and in the colitis model. me, the questions they asked refl ected a deep TCR repertoires compared to Tregs in the spleen and lymph nodes. level of understanding and gave me some • Jeffrey Bluestone (UCSF) presented new insights about own my work. Importantly, Tregs in adipose tissue fi ndings on the association between the instability of Foxp3 in Tregs with the Following the conference, I made my way onset of autoimmunity. At the peak of infl ammation in EAE, there is a high to San Francisco where I visited a few labs percentage of Tregs losing their Foxp3 at UCSF, which was another highlight of the expression. In contrast to that, the trip. I was excited when Qizhi Tang invited population of unstable Tregs decreases me to attend the joint lab meeting of the Tang and an increase in the percentage of and Jeffrey Bluestone’s labs, where I learnt Tregs that stably express Foxp3 is about the research currently conducted in found during the recovery stage. their labs. After the lab meeting, I presented my work to the UCSF tolerance group, which consists of Qizhi Tang’s, Jeffrey Bluestone’s, 34 ASI Inc. Newsletter June 2011

Keystone Symposium – B cells: New Insights into Normal versus Dysregulated Function Whistler, Canada , April 12–17, 2011 Dominique Gatto Garvan Institute of Medical Research, Sydney

Travel journal lab on this process, which included the I am not a diary person, my last attempt at role of new molecules, identifi ed by the keeping a journal ended nearly as soon as it powerful ENU genetic screens, such as began. Yet, I set out to my trip to the B cell ATP11c, Card11 and DOCK8, as well Keystone symposium “New Insights into as mechanisms of regulation of the B Mark Anderson’s and Abul Abbas’s labs. Normal versus Dysregulated Function” in cell receptor in tolerance induction. This Although I had already presented my work Whistler, Canada, with the intent of diligently inspiring talk ended with a vision of where in front of other scientists quite a few times, keeping a daily record of my experiences we hope to be in another 50 years after the it was extremely nerve-racking to speak in to be able to remember and share them on Burnet and Medawar Nobel prize, namely front of so many renowned immunologists. my return. in a position not only to understand how Fortunately, my presentation went smoothly lymphocytes select (or not) to mount the and received much positive feedback. It was Tuesday April 12 correct response and are activated or also very benefi cial for me to meet with the After a long journey I arrived in Whistler, a tolerised but, more importantly, to be able members of those labs who shared their mountain town approximately 2 hours drive to switch the response to cure disease. research fi ndings with me and also gave me a from Vancouver, known for hosting the better understanding on the lab environment Winter 2010 Olympics. The pretty scenery Wednesday April 13 and life in the US. with lakes, snow-coated mountains and We woke up to an unbelievably white fi r tree woods during the bus drive from morning; it was snowing, a sight that Overall, this trip has certainly given me Vancouver and the winter atmosphere in got many conference attendees excited, a lot of exposure as a scientist and has Whistler village was a re-discovered and even some Swiss-born like myself. But been a wonderful learning experience. The refreshing sight for my “Australia adapted” as today’s program promised a full day Keystone meeting was highly benefi cial to eyes so used to admiring the ocean. of interesting talks, little opportunity was my study and expanded my knowledge in left to enjoy the white delight. immunoregulation. Apart from the meeting, The opening of the conference, held visits to those famous labs were important in the Fairmont Chateau Hotel, was A personal highlight of this fi rst day was steps in developing my career as a researcher. preceded by refreshments, and just over 400 the session on germinal centre biology. During this trip, I was thrilled to fi nd out immunologists gathered for the welcome In particular, a Japanese group presented there were so many people who were highly and Keynote address. The strength of a novel BCL6 reporter mouse strain with interested in my work and also labs that are Australian immunology in the B cell fi eld data indicating that antigen-engaged B keen to receive me after the completion of was highlighted by a numerous delegation cells upregulated BCL6 before clustering my PhD. Of course, none of these could of Australian scientists and, most notably, in GCs and T cells expressed BCL6 come true if it was not for the invaluable by an Australian immunologist (one of the before interacting with B cells. In the help and funding from ASI, for which I am ones who “saw the light” and left the “dark evening plenary session, Facundo Batista extremely grateful. side” after spending a few years in the US, provided the fi rst evidence for a role for according to the introduction by David a cytoskeletal motor protein, Dynein, in Rawlings), Christopher Goodnow, giving moving B cell receptors on the plasma the Keynote address. membrane and showed data suggesting a function for iNKT cells in providing Chris Goodnow’s talk started with a bit help to B cells. of history on some of the discoveries that ASI Secretariat not only led to Nobel prizes but also had After being spoiled with “Lite Bites”, PO Box 7108, signifi cant “return on investment”, like the which for non-American standards Upper Ferntree Gully,Vic. 3156 use of monoclonal antibodies as drugs. In were closer to a full dinner, the poster Australia particular, he discussed the discoveries by session took place. Despite the full Tel: +61 3 9756 0128 Burnet and Medawar on clonal selection, day, the session was very well attended Fax: +61 3 9753 6372 which formed the basis of monoclonal and many interested attendees asking Email: [email protected] antibodies and the understanding of the questions came by at my poster until Offi ce hours: generation of immunity vs tolerance. The late in the night. 8.30am – 4.30pm mechanisms underlying the decision of lymphocyte activation vs tolerance are Thursday April 14 still poorly understood and this was one of The program again offered an interesting the main themes of the conference. Prof. variety of talks based on both mouse Goodnow presented new insights from his and human research. In the morning

35 ASI Inc. Newsletter June 2011

plenary session Andrea Cerutti presented to defi ne this population or a difference performed his famous lymphocyte rap, an fi ndings suggesting that human splenic between mice and humans. interpretation on the function of the immune neutrophils regulate innate B cell memory system that can even be found YouTube. by undergoing functional reprogramming Friday April 15 in response to bacterial signals. In The morning plenary session offered a great The good balance of presentations based a talk from Michael Cancro’s lab, a line-up of speakers and very interesting on the study of mouse models and talks novel population of innate-like B cells presentations around the theme of the showing human data was one of the big (ABCs, “Age-associated B cells”) was germinal centre reaction and B cell memory. strengths of this meeting, which offered a described, confi rming the results from However, what most attendees were probably varied yet focused array of fascinating talks a study presented the previous day. This most looking forward to today was the around the theme of normal vs dysregulated population of B cells present in both opportunity to go skiing or snowboarding B cell function. I am sure that, like me, many mice and humans was shown to expand during the long lunch break. The conditions young immunologists will return to their with age and be associated with the could not have been more optimal since it daily lab routines motivated and inspired by development of autoimmunity. Another had been snowing the last few days and the this meeting and I can only recommend this presentation that caught my interest sun was shining. Those who did not enjoy meeting series, for its topics and the excellent described a novel mouse reporter strain the afternoon on the skis had the chance to platform its size offers for discussions and for IgE, which offered a new tool to follow try and spot a bear by going for a walk in interactions. The wonderful surroundings IgE responses and demonstrated that, the woods. In fact, Whistler and Blackcomb clearly contributed to enjoyment of the trip contrary to previous belief, IgE+ cells Mountains support a population of up to 50 which, for many lucky attendees like myself, were present in germinal centres. Black bears that have adapted to feeding, will continue with a little exploration of mating, and hibernating amongst ski area this part of Canada. However, I am afraid While question time had usually been habitats (see picture). Unfortunately (or my writing of a travel journal, which only very friendly at this meeting (in contrast fortunately …) I cannot share the experience just started, will also end with this part of to the highly entertaining but rather of meeting one. the journey… aggressive questions/comments from leading immunologists at the previous B Saturday April 16 Last but not least, I would like to thank ASI for cell conference), a heated disagreement Much of the talks on this last day revolved supporting my attendance to this conference took place between Claudia Berek and around the role and manipulation of B cells in and continuing to give young researchers Bertrand Huard on whether to call the human autoimmunity and immunodefi ciency, the opportunity to travel to international newly discovered population of cells with interesting presentations on BAFF conferences. producing APRIL and mediating survival inhibition in SLE (Anne Davidson), of plasma cells in the bone marrow immununopathogenesis of B cells in HIV “eosinophil” or “myeloid precursor”. infection (Susan Moir) and the human It remains unclear to me whether the response to H1N1 infl uenza virus (Patrick difference was due to the markers used Wilson). As a special guest, Shiv Pillai Contributions sought for the ASI Newsletter You could win $200 !! Whistler Black Bear Deadline for the next issue : 1st August 2011

Please email your contributions to the Secretariat by the above date. [email protected]

36 ASI Inc. Newsletter June 2011

37 ASI Inc. Newsletter June 2011 Publications List Congratulations to ASI members who have published their following work in the last three months (articles with an ePub date between January and March 2011) Engwerda CR, Meeusen EN. Parasites and the infl ammation. J Autoimmun 2011; 36(1): 76. immunoglobulin E cross-reactivity between Pas n 1 immune system: a perspective from down under. of Bahia grass pollen and other group 1 grass pollen Petrovsky N, Ross TM. Challenges in improving Parasite Immunol 2010; 32(8): 529. allergens. Clin Exp Allergy 2011; 41(2): 281. infl uenza vaccine protection in the elderly. Expert Hein WR, Pernthaner A, Piedrafi ta D, Meeusen Rev Vaccines 2011; 10(1): 7. Ewing P, Otczyk DC, Occhipinti S, Kyd JM, Gleeson EN. Immune mechanisms of resistance to M, Cripps AW. Developmental profi les of mucosal Reece P, Thanendran A, Crawford L, Tulic MK, gastrointestinal nematode infections in sheep. immunity in pre-school children. Clin Dev Immunol Thabane L, Prescott SL, Sehmi R et al. Maternal Parasite Immunol 2010; 32(8): 541. 2010; 2010: 196785. allergy modulates cord blood hematopoietic de Veer M, Kemp J, Chatelier J, Elhay MJ, progenitor Toll-like receptor expression and function. Upham JW, James AL. Remission of asthma: The Meeusen EN. The kinetics of soluble and J Allergy Clin Immunol 2011; 127(2): 447. next therapeutic frontier? Pharmacol Ther 2011; particulate antigen traffi cking in the afferent 130(1): 38. Cox JH, Kljavin NM, Ramamoorthi N, Diehl L, lymph, and its modulation by aluminum-based Batten M, Ghilardi N. IL-27 promotes T cell- McGee HM, Malley RC, Muller HK, Woods GM. adjuvant. Vaccine 2010; 28(40): 6597. dependent colitis through multiple mechanisms. J Neonatal exposure to UVR alters skin immune Abeynaike L, Meeusen EN, Bischof RJ. An Exp Med 2011; 208(1): 115. system development, and suppresses immunity in ovine tracheal explant culture model for allergic adulthood. Immunol Cell Biol 2011. Every AL, Stent A, Moloney MB, Ng GZ, Skene airway infl ammation. J Infl amm (Lond) 2010; CD, Edwards SJ, Sutton P. Evaluation of superoxide Deleyrolle LP, Ericksson G, Morrison BJ, Lopez JA, 7: 46. dismutase from Helicobacter pylori as a protective Burrage K, Burrage P, Vescovi A et al. Determination de Silva K, Begg D, Whittington R. The vaccine antigen. Vaccine 2011; 29(7): 1514. of somatic and cancer stem cell self-renewing interleukin 10 response in ovine Johne’s disease. symmetric division rate using sphere assays. PLoS Robinson N, Pleasance J, Piedrafi ta D, Meeusen EN. Vet Immunol Immunopathol 2011; 139(1): 10. One 2011; 6(1): e15844. The kinetics of local cytokine and galectin expression Piedrafi ta D, Raadsma HW, Gonzalez J, Meeusen after challenge infection with the gastrointestinal Stewart TJ, Smyth MJ. Improving cancer E. Increased production through parasite control: nematode, Haemonchus contortus. Int J Parasitol immunotherapy by targeting tumor-induced immune can ancient breeds of sheep teach us new 2011; 41(5): 487. suppression. Cancer Metastasis Rev 2011; 30(1): lessons? Trends Parasitol 2010; 26(12): 568. 125. Ahlgren KM, Moretti S, Lundgren BA, Karlsson Williams SA, Harata-Lee Y, Comerford I, I, Ahlin E, Norling A, Hallgren A et al. Increased Sou T, Meeusen EN, de Veer M, Morton DA, Anderson RL, Smyth MJ, McColl SR. Multiple IL-17A secretion in response to Candida albicans in Kaminskas LM, McIntosh MP. New developments functions of CXCL12 in a syngeneic model of autoimmune polyendocrine syndrome type 1 and its in dry powder pulmonary vaccine delivery. Trends breast cancer. Mol Cancer 2010; 9: 250. animal model. Eur J Immunol 2011; 41(1): 235. Biotechnol 2011; 29(4): 191. Kreiss A, Tovar C, Obendorf DL, Dun K, Steinmetz OM, Summers SA, Gan PY, Semple T, Davies JM, Voskamp A, Dang TD, Pettit B, Loo D, Woods GM. A murine xenograft model for a Holdsworth SR, Kitching AR. The Th17-defi ning Petersen A, Hill MM et al. The dominant 55 kDa transmissible cancer in Tasmanian devils. Vet transcription factor RORgammat promotes allergen of the subtropical Bahia grass (Paspalum Pathol 2011; 48(2): 475. glomerulonephritis. J Am Soc Nephrol 2011; 22(3): notatum) pollen is a group 13 pollen allergen, Pas n Lichtfuss GF, Meehan AC, Cheng WJ, Cameron 472. 13. Mol Immunol 2011; 48(6-7): 931. PU, Lewin SR, Crowe SM, Jaworowski A. HIV Carroll ML, Yerkovich ST, Pritchard AL, Davies JM, Gonzalez JF, Hernandez A, Meeusen EN, Rodriguez inhibits early signal transduction events triggered Upham JW. Adaptive immunity to rhinoviruses: sex F, Molina JM, Jaber JR, Raadsma HW et al. by CD16 cross-linking on NK cells, which and age matter. Respir Res 2010; 11: 184. Fecundity in adult Haemonchus contortus parasites are important for antibody-dependent cellular is correlated with abomasal tissue eosinophils and Kyd JM, McGrath J, Krishnamurthy A. Mechanisms cytotoxicity. J Leukoc Biol 2011; 89(1): 149. gammadelta T cells in resistant Canaria Hair Breed of bacterial resistance to antibiotics in infections of sheep. Vet Parasitol 2011. Comerford I, Bunting M, Fenix K, Haylock- COPD patients. Curr Drug Targets 2011; 12(4): 521. Jacobs S, Litchfi eld W, Harata-Lee Y, Turvey Riedmann EM, Lubitz W, McGrath J, Kyd JM, Purdie AC, Plain KM, Begg DJ, de Silva K, M et al. An immune paradox: how can the same Cripps AW. Effectiveness of engineering the Whittington RJ. Candidate gene and genome-wide chemokine axis regulate both immune tolerance nontypeable Haemophilus infl uenzae antigen Omp26 association studies of Mycobacterium avium subsp. and activation?: CCR6/CCL20: a chemokine as an S-layer fusion in bacterial ghosts as a mucosal paratuberculosis infection in cattle and sheep: A axis balancing immunological tolerance and vaccine delivery. Hum Vaccin 2011; 7: 99. review. Comp Immunol Microbiol Infect Dis 2011; infl ammation in autoimmune disease. Bioessays 34(3): 197. Summers SA, Phoon RK, Ooi JD, Holdsworth SR, 2010; 32(12): 1067. Kitching AR. The IL-27 receptor has biphasic effects Sterjovski J, Churchill MJ, Roche M, Ellett A, Tate MD, Brooks AG, Reading PC. Correlation in crescentic glomerulonephritis mediated through Farrugia W, Wesselingh SL, Cunningham AL et al. between sialic acid expression and infection Th1 responses. Am J Pathol 2011; 178(2): 580. CD4-binding site alterations in CCR5-using HIV-1 of murine macrophages by different strains of envelopes infl uencing gp120-CD4 interactions and Teng MW, von Scheidt B, Duret H, Towne JE, Smyth infl uenza virus. Microbes Infect 2011; 13(2): 202. fusogenicity. Virology 2011; 410(2): 418. MJ. Anti-IL-23 monoclonal antibody synergizes Bertin-Maghit S, Pang D, O’Sullivan B, Best S, in combination with targeted therapies or IL-2 to Agostino M, Sandrin MS, Thompson PE, Farrugia Duggan E, Paul S, Thomas H et al. Interleukin- suppress tumor growth and metastases. Cancer Res W, Ramsland PA, Yuriev E. Carbohydrate-mimetic 1beta produced in response to islet autoantigen 2011; 71(6): 2077. peptides: structural aspects of mimicry and presentation differentiates T-helper 17 cells at the therapeutic implications. Expert Opin Biol Ther Kitching AR, Holdsworth SR. The emergence of expense of regulatory T-cells: Implications for 2011; 11(2): 211. TH17 cells as effectors of renal injury. J Am Soc the timing of tolerizing immunotherapy. Diabetes Nephrol 2011; 22(2): 235. 2011; 60(1): 248. Vesely MD, Kershaw MH, Schreiber RD, Smyth MJ. Natural innate and adaptive immunity to cancer. Stagg J, Divisekera U, Duret H, Sparwasser T, Tulic MK, Hodder M, Forsberg A, McCarthy Annu Rev Immunol 2011; 29: 235. Teng MW, Darcy PK, Smyth MJ. CD73-Defi cient S, Richman T, D’Vaz N, van den Biggelaar AH Mice Have Increased Antitumor Immunity and Are et al. Differences in innate immune function Win SJ, Ward VK, Dunbar PR, Young SL, Baird MA. Resistant to Experimental Metastasis. Cancer Res between allergic and nonallergic children: new Cross-presentation of epitopes on virus-like particles 2011; 71(8): 2892. insights into immune ontogeny. J Allergy Clin via the MHC I receptor recycling pathway. Immunol Immunol 2011; 127(2): 470. Cell Biol 2011. Sluyter R, Stokes L. Signifi cance of P2X7 receptor variants to human health and disease. Recent Pat McKelvey KJ, Highton J, Hessian PA. Cell- Davies JM, Dang TD, Voskamp A, Drew AC, DNA Gene Seq 2011; 5(1): 41. specifi c expression of TLR9 isoforms in Biondo M, Phung M, Upham JW et al. Functional

38 ASI Inc. Newsletter June 2011

Al-Ejeh F, Smart CE, Morrison BJ, Chenevix- combined with immune-stimulating antibodies. Proc Ngiow SF, von Scheidt B, Akiba H, Yagita H, Trench G, Lopez JA, Lakhani SR, Brown MP et al. Natl Acad Sci U S A 2011; 108(10): 4141. Teng MW, Smyth MJ. Anti-TIM3 Antibody Breast cancer stem cells: treatment resistance and Promotes T Cell IFN-{gamma}-Mediated Cretney E, Xin A, Shi W, Minnich M, Masson F, therapeutic opportunities. Carcinogenesis 2011; Antitumor Immunity and Suppresses Established Miasari M, Belz GT et al. The transcription factors 32(5): 650. Tumors. Cancer Res 2011; 71(10): 3540. Blimp-1 and IRF4 jointly control the differentiation Every AL, Selwood L, Castano-Rodriguez N, Lu and function of effector regulatory T cells. Nat Salwati E, Minigo G, Woodberry T, Piera KA, W, Windsor HM, Wee JL, Swierczak A et al. Did Immunol 2011; 12(4): 304. de Silva HD, Kenangalem E, Tjitra E et al. transmission of Helicobacter pylori from humans Differential cellular recognition of antigens Tovar C, Obendorf D, Murchison EP, Papenfuss AT, cause a disease outbreak in a colony of Stripe-faced during acute Plasmodium falciparum and Kreiss A, Woods GM. Tumor-Specifi c Diagnostic Dunnarts (Sminthopsis macroura)? Vet Res 2011; Plasmodium vivax malaria. J Infect Dis 2011; Marker for Transmissible Facial Tumors of 42(1): 26. 203(8): 1192. Tasmanian Devils: Immunohistochemistry Studies. Petrovsky N. The vaccine renaissance. Hum Vaccin Vet Pathol 2011. Whittington RJ, Begg DJ, de Silva K, Plain KM, 2011; 7(2). Purdie AC. Comparative immunological and Carroll KE, Dean MM, Heatley SL, Meehan AC, microbiological aspects of paratuberculosis as Pleasance J, Raadsma HW, Estuningsih SE, Mifsud NA, Kotsimbos TC, Snell GI et al. High a model mycobacterial infection. Vet Immunol Widjajanti S, Meeusen E, Piedrafi ta D. Innate and Levels of Mannose-Binding Lectin Are Associated Immunopathol 2011. adaptive resistance of Indonesian Thin Tail sheep With Poor Outcomes After Lung Transplantation. to liver fl uke: A comparative analysis of Fasciola Transplantation 2011; 91(9): 1044. Fasquelle L, Scott HS, Lenoir M, Wang J, gigantica and Fasciola hepatica infection. Vet Rebillard G, Gaboyard S, Venteo S et al. Haylock-Jacobs S, Comerford I, Bunting M, Kara E, Parasitol 2011. Tmprss3, a Transmembrane Serine Protease Townley S, Klingler-Hoffmann M, Vanhaesebroeck Defi cient in Human DFNB8/10 Deafness, Is Amos SM, Pegram HJ, Westwood JA, John LB, B et al. PI3Kdelta drives the pathogenesis of Critical for Cochlear Hair Cell Survival at the Devaud C, Clarke CJ, Restifo NP et al. Adoptive experimental autoimmune encephalomyelitis by Onset of Hearing. J Biol Chem 2011; 286(19): immunotherapy combined with intratumoral TLR inhibiting effector T cell apoptosis and promoting 17383. agonist delivery eradicates established melanoma in Th17 differentiation. J Autoimmun 2011; 36(3-4): mice. Cancer Immunol Immunother 2011; 60(5): 671. 278. Telwatte S, Moore K, Johnson A, Tyssen D, Sterjovski J, Aldunate M, Gorry PR et al. Comerford I, McColl SR. Mini-review series: focus McGuckin MA, Linden SK, Sutton P, Florin TH. Virucidal activity of the dendrimer microbicide on chemokines. Immunol Cell Biol 2011; 89(2): 183. Mucin dynamics and enteric pathogens. Nat Rev SPL7013 against HIV-1. Antiviral Res 2011; Microbiol 2011; 9(4): 265. Roberts TL, Dunn JA, Sweet MJ, Hume DA, 90(3): 195. Stacey KJ. The immunostimulatory activity of Gruber-Wackernagel A, Heinemann A, Konya Hutchinson AT, Alexova R, Bockhorni V, phosphorothioate CpG oligonucleotides is affected V, Byrne SN, Singh TP, Hofer A, Legat F et al. Ramsland PA, Jones DR, Jennings CV, by distal sequence changes. Mol Immunol 2011; Photohardening restores the impaired neutrophil Broady K et al. Characterization of a unique 48(8): 1027. responsiveness to chemoattractants leukotriene B4 conformational epitope on free immunoglobulin and formyl-methionyl-leucyl-phenylalanin in patients Butcher CM, Neufi ng PJ, Eriksson L, Carmichael kappa light chains that is recognized by an with polymorphic light eruption. Exp Dermatol 2011; CL, Wilkins EJ, Melo JV, Lewis ID et al. RUNX1 antibody with therapeutic potential. Mol 20(6): 473. mutations are rare in chronic phase polycythaemia Immunol 2011; 48(9-10): 1245. vera. Br J Haematol 2011; 153(5): 672. Slatter TL, Hung N, Campbell H, Rubio C, Mehta Ling KH, Brautigan PJ, Hahn CN, Daish T, R, Renshaw P, Williams G et al. Hyperproliferation, Croft NP, Purcell AW. Peptidomimetics: modifying Rayner JR, Cheah PS, Raison JM et al. Deep cancer, and infl ammation in mice expressing a peptides in the pursuit of better vaccines. Expert Rev sequencing analysis of the developing mouse {Delta}133p53-like isoform. Blood 2011; 117(19): Vaccines 2011; 10(2): 211. brain reveals a novel microRNA. BMC Genomics 5166. Drini M, Wong NC, Scott HS, Craig JM, Dobrovic A, 2011; 12: 176. Broadley KW, Hunn MK, Farrand KJ, Price Hewitt CA, Dow C et al. Investigating the potential Greer JM, McCombe PA. Role of gender in KM, Grasso C, Miller RJ, Hermans IF et al. Side role of genetic and epigenetic variation of DNA multiple sclerosis: Clinical effects and potential population is not necessary or suffi cient for a cancer methyltransferase genes in hyperplastic polyposis molecular mechanisms. J Neuroimmunol 2011; stem cell phenotype in glioblastoma multiforme. syndrome. PLoS One 2011; 6(2): e16831. 234(1-2): 7. Stem Cells 2011; 29(3): 452. Roche M, Jakobsen MR, Sterjovski J, Ellett A, Posta Penko D, Mohanasundaram D, Sen S, Campbell IK, van Nieuwenhuijze A, Segura E, F, Lee B, Jubb B et al. HIV-1 Escape from the CCR5 Drogemuller C, Mee C, Bonder CS, Coates PT et O’Donnell K, Coghill E, Hommel M, Gerondakis S Antagonist Maraviroc Associated with an Altered al. Incorporation of endothelial progenitor cells et al. Differentiation of Infl ammatory Dendritic Cells and Less-Effi cient Mechanism of gp120-CCR5 into mosaic pseudoislets. Islets 2011; 3(3): 73. Engagement That Attenuates Macrophage Tropism. J Is Mediated by NF-{kappa}B1-Dependent GM-CSF Zamudio NM, Scott HS, Wolski K, Lo CY, Law Virol 2011; 85(9): 4330. Production in CD4 T Cells. J Immunol 2011; 186(9): 5468. C, Leong D, Kinkel SA et al. DNMT3L Is a Shah N, Steptoe RJ, Parekh HS. Low-generation Regulator of X Chromosome Compaction and Tan S, Gordon DL, Honda-Okubo Y, Petrovsky N, asymmetric dendrimers exhibit minimal toxicity and Post-Meiotic Gene Transcription. PLoS One Phillips P, Huddleston S, Sadlon TA. Serological effectively complex DNA. J Pept Sci 2011; 17(6): 2011; 6(3): e18276. 470. responses following infl uenza A H1N1 2009 infection in adults. J Infect 2011. Vujanic A, Sutton P, Snibson KJ, Yen HH, Singh P, Yan J, Hull R, Read S, O’Sullivan Scheerlinck JP. Mucosal vaccination: Lung Tate MD, Ioannidis LJ, Croker B, Brown LE, Brooks J, Henderson RD, Rose S et al. Levels of versus nose. Vet Immunol Immunopathol 2011. phosphorylated axonal neurofi lament subunit H AG, Reading PC. The role of neutrophils during mild Ao A, Morrison BJ, Wang H, Lopez JA, (pNfH) are increased in acute ischemic stroke. J and severe infl uenza virus infections of mice. PLoS Reynolds BA, Lu J. Response of estrogen Neurol Sci 2011; 304(1-2): 117. One 2011; 6(3): e17618. receptor-positive breast cancer tumorspheres to Broadley K, Larsen L, Herst PM, Smith RA, Tate MD, Job ER, Brooks AG, Reading PC. antiestrogen treatments. PLoS One 2011; 6(4): Berridge MV, McConnell MJ. The novel Glycosylation of the hemagglutinin modulates the e18810. sensitivity of H3N2 infl uenza viruses to innate phloroglucinol derivative PMT7 kills glycolytic Douradinha B, Doolan DL. Harnessing immune proteins in airway secretions and virulence in mice. cancer cells by blocking autophagy and sensitising to responses against Plasmodium for rational Virology 2011; 413(1): 84. nutrient stress. J Cell Biochem 2011. vaccine design. Trends Parasitol 2011. Yuriev E, Agostino M, Ramsland PA. Challenges and Gruber-Wackernagel A, Bambach I, Legat FJ, Hofer advances in computational docking: 2009 in review. A, Byrne SN, Quehenberger F, Wolf P. Randomized J Mol Recognit 2011; 24(2): 149. double-blinded placebo-controlled intra-individual trial on 1,25-(OH)2 vitamin D3 analogue in Christiansen AJ, West A, Banks KM, Haynes NM, polymorphic light eruption. Br J Dermatol 2011. Teng MW, Smyth MJ, Johnstone RW. Eradication of solid tumors using histone deacetylase inhibitors

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