NEWSLETTER

Australasian Society for Incorporated PP 341403100035 ISSN 1442-8725 June 2006

Overview of the JCSMR Immunogenomics Laboratory 2006 Gerard Hoyne

Overview they were able to reveal that the autoimmune but Dr Horikawa, a postodoctoral fellow in The Immunogenomics Laboratory at the regulator gene AIRE, which is expressed by the lab, has made the remarkable fi nding that John Curtin School of Medical Research in a subset of thymic epithelial cells, plays a the exact opposite is the case. The memory Canberra comprises four research groups critical role in establishing T cell tolerance B cell receptor is less active at inducing a working in concert to develop an integrated to self antigens in the thymus. In addition, subset of genes, and in this case less signal understanding of how our immune system is Adrian also identifi ed that defective signals means more antibody formation. controlled at the cellular and molecular level to cell death genes account for the inherited by circuits that are specifi ed in our genome resistance of T lymphocytes to clonal deletion Carola Vinuesa heads the Humoral sequence. Each of the groups focuses on in the thymus of NOD mice. Upon infection memory and Autoimmunity Group. a different element of a fundamental set with a virus or bacteria, B lymphocytes with Her group is investigating the cellular and of immune system decisions made at the the right antigen receptors to neutralize molecular events that regulate production level of individual immune system cells: infection are stimulated to switch the isotype and selection versus elimination of memory either to fi ght or to disarm. The process of of their receptor from IgM to IgG, and at the B cells which is of critical importance to deciding which immune cells should fi ght same time secretion of antibodies by these understand how best to harness immune and which should disarm is key to our ability switched cells is dramatically increased. responses against infection, and to mitigate to resist infection and parasitism. Mistakes A previous PhD student, Dr Steve Martin, against autoimmunity. One approach in this process result in incurable infections, discovered that the switched receptor – and utilised by Vinuesa’s group is to survey autoimmune diseases, allergy, lymphoma, indeed a small tail segment uniquely found the mammalian genome by ENU mouse and leukaemia. Moreover, drugs and other in switched receptors – explains the dramatic mutagenesis to identify single point ways to alter fi ght or disarm decisions are elevation of antibody secretion that serves mutations that predispose to systemic sorely needed to improve the success of organ as the cardinal measure of immunological transplantation and treatment of autoimmune memory. It was thought that the IgG tail cont. p4 diseases and metastatic cancer. would enhance antibody production by enhancing a signal within B lymphocytes, Contents For a long time it was not possible to see how memory and effector cells are JCSMR Immunogenetics Laboratory 1 made, nor how self-reactive lymphocytes disarm themselves. The Immunogenomics Editorial 3 Laboratory headed by Chris Goodnow has Day of Immunology 2006 3 pioneered ways to visualize these processes Treasurer’s Report on Audit 3 in genetically modifi ed transgenic mice. By studying cells from the transgenic mice, SIG Mucosal Immunology Update 5 we have discovered that each immune cell Councillors' News 6 must run through a complex series of fi ght 2004–2005 Audit Report 8 or disarm checkpoints before it can be fully ASI Student Page 12 launched into an immune response. In some ways, the process resembles the sequence of 2006 ASI Conference 13 fi ght/disarm decisions in a military missile Comments from ASI Members 16 launch, which serve a similar purpose of An Immunological Saga 17 preventing friendly fi re and optimising targeting against invaders. Together with Upcoming Lectures & Conferences 20 Adrian Liston a former PhD student in the lab Chris Goodnow ASI Inc. Newsletter June 2006

ASI Inc. COUNCIL

President Vice President Dr Philip Hodgkin Professor Alan Baxter Non-Voting Councillors: Walter & Eliza Hall Institute CGC, James Cook University 1G Royal Parade Townsville Qld 4811 Newsletter Editor Parkville Vic 3050 Ph: 07 4781 6265 Fax: 07 4781 6078 Dr Miles Davenport Ph: 02 9385 2762 Fax: 02 9385 1389 Ph: 03 9345 2609 Fax: 03 9347 0852 Email: [email protected] Email: [email protected] Email: [email protected] Journal Editor Professor Chris Parish Honorary Secretary Honorary Treasurer Ph: 02 6125 2604 Fax: 02 6125 2595 Dr Jose Villadangos Dr Norbert Kienzle Email: [email protected] Walter & Eliza Hall Institute Queensland Institute of Medical Research 1G Royal Parade 300 Herston Road Visiting Speakers Co-ordinator Parkville Vic 3050 Brisbane Qld 4006 A/Prof J. Alejandro Lopez Ph: 03 9345 2532 Fax: 03 9347 0852 Ph: 07 3362 0379 Fax: 07 3362 0105 Queensland Institute of Medical Research Email: villadangos@.edu.au Email: [email protected] CBCRC/I, Post Offi ce Royal Brisbane Hospital Qld 4029 Ph: 07 3845 3794 Fax: 07 3845 3510 State Councillors Email: Email: [email protected] New South Wales Victoria & Tasmania Council Member of IUIS Dr Bernadette Saunders Dr Phillip Darcy Professor Chris Parish Ph: 02 9565 6114 Fax: 02 9565 6101 Ph: 03 9656 3769 Fax: 03 9656 1411 Ph: 02 6125 2604 Fax: 02 6125 2595 Email: [email protected] Email: [email protected] Email: [email protected]

Honorary Archivist & Webmaster: Queensland South Australia & Northern Territory Dr Judith Greer Dr Christopher Schmidt Dr Claudine Bonder Ph: 07 3365 5133 Fax: 07 3365 5462 Ph: 07 3362 0313 Fax: 07 3362 3510 Ph: 08 8222 3852 Fax: 08 8232 4092 Email: [email protected] Email: [email protected] Email: [email protected] Administrative Correspondence Western Australia Australian Capital Territory Ms Judi Anderson Dr Chris Andoniou Dr Guna Karupiah ASI Inc. Secretariat Ph: 08 9381 0799 Fax: 08 9381 0700 Ph: 02 6125 4562 Fax: 02 6125 2595 PO Box 7108 Email: [email protected] Email: [email protected] Upper Ferntree Gully Vic 3156 Ph: 03 9756 0128 Fax: 03 9753 6372 New Zealand Email: [email protected] Prof John Fraser Ph: +64 9 373 7599 ext 86036 Fax: +64 9 373 8774 Email: [email protected]

FIMSA Councillor Contact for Tasmania Professor Nicholas King Dr Greg Woods Ph: 02 9351 4553 Fax: 02 9351 3429 Tel: 03 6226 4830 Fax: 03 6226 4833 Email: [email protected] 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 j.greer@medicine. uq.edu.au

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2 ASI Inc. Newsletter June 2006

EDITORIAL The Day of Treasurer’s report Immunology – on the Financial This quarter’s newsletter brings exciting details of the upcoming annual conference April 29, 2006 Audit for ASI for in Auckland in December. A list of speakers For the second consecutive year the European is included on pages 13-15, and conference Federation of Immunological Societies 2004/2005 details can be found at the website below. (EFIS) has organised the Day of Immunology (DoI) on April 29. This year, the emphasis ASI passed its inaugural fi nancial audit A new addition to the newsletter is the was on delivering information about the with fl ying colours. As stated previously annual audit of ASI’s fi nances (p8-11). The discipline of Immunology to school kids. to the membership, record growth Council thought it important to share this with Most of the activities took place in Germany (note, not net) income and Victorian members so we can all know our membership (Berlin, Hannover, Munich, Erlangen) and Government laws made it necessary that funds are being managed well. If reading Denmark and included conferences and ASI underwent an independent audit for this is not enough of a challenge, we also meetings of general interest dealing with the fi nancial year from 1 November 2004 have our fi rst “immunology crossword” by subjects such as antibody-therapy, avian to 31 October 2005. Margaret Crossley our student representative Amanda Taylor infl uenza and multiple sclerosis. from WHK Day Neilson in (p12) to test your mental agility. undertook the audit and her fi ndings The main project was the launching of are to be found on pages 8–11 of this Finally, some refl ections by Tony Basten on the prize for “Partners in Immunology newsletter . pages 17-20. Tony retired as director of the and Education” (PIE) which will reward Centenary Institute earlier this year and his proposals fostering the interactions between As stated in the summary of income article is a very humorous and interesting research institutes and schools that facilitate and expenditure, ASI has a total of recount of his adventures during a life in the understanding of Immunology by school $333,743 in accumulated funds including immunology. children. The prize of €1500 will be awarded a surplus of $50,520. These fi gures are during the coming European Immunology slightly higher as the ones stated in Miles Davenport Congress in Paris (Sept. 2006). the Treasurer’s Report in the minutes of the AGM 2005 (printed in the last This year, the president of the International issue of the Newsletter); however the Union of Immunological Societes (IUIS), AGM calculations refl ected operational Rolf Zinkernagel made an appeal to all accumulated funds and surplus including societies to join a coordinated International a pre-existing commitment of ~$24,000 effort to promote public awareness for for the annual ASI branch funding. Immunology in a Global Day of Immunology on April 29 2007. Overall ASI Council is very grateful to Margaret for her professional assessment A report from the founder of the initiative and has decided on an annual fi nancial Stefan Kaufman was recently published in audit for the future. Immunity 24,349, 2006. Further details on Contributions the initiative can be found in http://www. Norbert Kienzle Honorary Treasurer sought for the dayofi mmunology.org ASI Newsletter You could win $100 !! Deadline for the Sustaining next issue : 2006 ASI annual conference 1st August 2006 Auckland, New Zealand Membership December 3–7, 2006. ASI Inc acknowledges the Please email your contributions www.asi2006.auckland.ac.nz support of the following to the Secretariat by the sustaining members: above date. • Jomar Diagnostics [email protected] • Dynal Biotech Pty Ltd

3 ASI Inc. Newsletter June 2006

Overview of the JCSMR Immunogenomics Laboratory 2006 (cont)

Carola Gerard Ed Vinuesa Hoyne Bertram

autoimmune disease. This screen has Development and Regulation Group. The A unique collection of C57BL/6 mouse led to the discovery of Roquin, a key main emphasis of Gerard’s group has been libraries at the Australian Phenomics piece in what appears to be a crucial involved in a genome wide ENU mutagenesis Facility, bearing chemically induced single pathway for repressing formation of screen to identify new autoimmune variant DNA changes across the genome have been lupus autoantibodies through regulating genes that predispose to organ-specifi c undergoing a systematic screen to identify the function of T follicular helper autoimmune disease using a transgenic pedigrees with genes controlling lymphocyte

(TFH) cells. Work by Dr Diego Silva, a model of type1 diabetes. Through a joint development and migration, autoimmunity, postdoctoral fellow, has revealed Roquin NH&MRC/JDRF funded program grant humoral immune responses, and NK cells. also plays a critical role in peripheral T more than 40 new strains that develop type1 The large-scale project involves Chris cell tolerance to pancreatic antigens and diabetes have been identifi ed and several Goodnow and Carola Vinuesa’s groups as is a potent suppressor of autoimmune of these have entered mapping. In addition well as Drs Lewis Lanier, Art Weiss, Jason diabetes. Carola’s group is now also two strains have been identifi ed that develop Cyster from University of California San investigating whether genetic defects in obesity and type 2 diabetes. Other interests Francisco. Ed will make use of some of the Roquin pathway may account for a in the group is associated with the role of these libraries to embark on an a new ENU fraction of patients with SLE or type 1 Notch signaling during T cell development screen to identify genes that regulate the diabetes. This work is being carried out exploring the link between Notch and Ikaros development of CD8 T cell memory and by Michelle Linterman, a PhD student, in in the development of T cell leukaemia, and recall to infl uenza virus. collaboration with John Harley (OMRF, in collaboration with Dr Sally Dunwoodie US). In partnership with Dr Matthew at the Victor Chang Cardiac Institute in PhD positions and other research opportunities Cook, they have launched in the last , we have been investigating the exist for scientists wishing to join these year the “APOSLE” study, with the function of the Notch ligand Delta3 in the groups. More information on individual aims of establishing an Australian DNA immune system. groups can be found at: collection from patients with SLE that can be screened for mutations in candidate Ed Bertram is the leader of the Anti-Viral Chris’s lab web page: lupus genes. T cell Costimulation and Memory group http://immunogenomics.jcs.anu.edu.au which was established in 2005. Ed is also Carola’s lab web page: Finally, in order to elucidate the molecular currently the Head of Scientifi c Programs http://immunogenomics.jcs.anu.edu.au/ signals that regulate memory B cell at the Australian Phenomics Facility (www. staff/vinuesa.htm formation, Vinuesa’s group has also taken apf.edu.au). Ed’s main research interest is advantage of a model system in which in the regulation of CD8+ T cell immune Gerard’s lab web page: germinal centres can be produced without responses using infl uenza virus as a model http://immunogenomics.jcs.anu.edu.au/ T cells. After cell sorting and microarray pathogen and the role that costimulatory staff/hoyne.htm profi ling in collaboration with Professor molecules such as LIGHT:HVEM and 4- Ed’s lab web page: Ian MacLennan’s group (Birmingham, 1BBL:4-1BB, as well signals transduced http://immunogenomics.jcs.anu.edu.au/ UK), Di Yu has confi rmed the differential from costimulatory molecules via Carma-1 staff/bertram.htm pattern of expression of a group of genes infl uence the differentiation of CD8 + T found in normal centrocytes undergoing cells. This work has involved collaboration Recent Key Publications: T cell-driven selection, but not expressed with Dr Steve Turner and lab members at Miosge LA, Blasioli J, Blery M, Goodnow CC. in centrocytes from sterile germinal the University of Melbourne. Analysis of an Ethylnitrosourea-generated Mouse centres. Mutation Defi nes a Cell Intrinsic Role of Nuclear Factor kappaB2 in Regulating Circulating B Cell Gerard Hoyne leads the T Cell Numbers. J Exp Med 2002;196:1113-9

4 ASI Inc. Newsletter June 2006

Liston A, Lesage, S., Wilson J, Townsend M, Goodnow C. Organ-specific T cells escape SIG Mucosal Immunology Update thymic censoring as a result of autoimmune A very successful Mucosal Immunology highly likely that a limited number of polyendocrinopathy syndrome 1 mutation. Nat Immunol. 2003;4:350-354. Symposium took place at the ASI meeting travel bursaries would be available for held in Melbourne in December. The young Australian researchers to attend Jun J, Wilson, LE, Vinuesa, CG, Lesage, S., Symposium was attended by approximately the international meeting in Tokyo in Blery, M., Miosge, LA, Cook, MC, Kucharska, 130 of the conference delegates. Dr Hiroshi 2007. EM, Dolmanshenz, H, Hong, NA, Glynne, RJ, Hara, H, Penninger, JM, Nelms, KA, Goodnow, Kiyono, President of the International CC. Selectively crippled immunogenic responses Society for Mucosal Immunology, travelled There was general discussion concerning and atopy in mice with an ENU induced point from Japan to give the Key Symposium ways in which to advance the SIG and mutation in the PDZ protein Carma-1. Immunity talk on “A Potential New Mechanism for it was decided that a one-day mucosal 2003;18:751-76. the Induction of Orally Infused Tolerance.” immunology workshop would be Suh WK, Gajewska BU, Okada H, Gronski MA, The standard set by Dr Kiyono was followed proposed to coincide with the 2007 Bertram EM, Dawicki W, et al. The B7 family by engaging talks from Dorothee Bourges, ASI meeting. It is planned that this member B7-H3 preferentially downregulates Sanda Stankovic, Susan Johnson and Phil workshop will cover gut, respiratory Thelper 1-mediated immune responses. Nature. Sutton. and reproductive aspects of mucosal Immunol. 2003 4:899-906. immunity. In addition, the SIG will Papathanasiou P, Perkins AC, Cobb BS, Ferrini The Symposium was followed by a meeting continue to support the Graham Jackson R, Sridharan R, Hoyne GF, et al. Widespread of the Special Interest Group to decide on Memorial Poster Prize at the annual ASI failure of hematolymphoid differentiation caused the future directions of the Special Interest scientifi c meetings. by a recessive niche-fi lling allele of the Ikaros Group and on how Mucosal Immunology transcription factor. Immunity 2003;19:131-44. can be promoted more broadly in the ASI Allan Cripps was confirmed as the Liston A, Gray D, Lesage S, Fletcher A, Wilson membership. The Special Interest Group ongoing convenor of the Special Interest J, Webster K, et al. Gene Dosage–limiting Role in Mucosal Immunology was formed in Group and an Executive Committee of Aire in Thymic Expression, Clonal Deletion, 1993 and successfully lobbied for the was appointed to assist him with the and Organ-specifi c Autoimmunity. J Exp Med 9th International Congress of Mucosal organisation of the SIG and planning of 2004;200:1015-1026. Immunology, which was held in Sydney in the 2007 workshop. The SIG Executive Liston A, Lesage S, Gray D, O’Reilly L, Strasser A, August 1997. consists of: Fahrer A, et al. Generalized Resistance to Thymic Allan Cripps, convenor Deletion in the NOD Mouse: A Polygenic Trait Dr Kiyono briefed the meeting on his vision (allan.Cripps@griffi th.edu.au) Characterized by Defective Induction of Bim. for greater engagement with the International Ken Beagley Immunity 2004;21:817-830. Society and communicated that issues ([email protected]) Bertram EM, Dawicki W, Sedgmen B, Bramson JL, relating to the focus of Mucosal Immunology Margaret Dunkley Lynch DH, Watts TH. A switch in costimulation was not only a problem peculiar to our own ([email protected]) from CD28 to 4-1-BB during primary versus Special Interest Group. At the Melbourne Phil Sutton ([email protected]) secondary CD8 T cell response to infl uenza in meeting there were only three posters in vivo. J. Immunol. 2004 172: 981-988. Mucosal Immunology poster session and The SIG Executive Committee would Dawicki W, Bertram EM, Sharpe AH, Watts TH. it was obvious that Mucosal Immunology be delighted to receive suggestions and 4-1BB and OX40 act independently to facilitate related abstracts, particularly those relevant advice with respect to the SMI 2007 robust CD8 and CD4 recall responses. J. Immunol. to mucosal vaccines, had been placed in other meeting in Tokyo as well as the workshop 2004 173: 5944-5951. sessions. As a result, the SIG decided to planned for the ASI meeting in 2007. Vinuesa C, Goodnow CC. Illuminating extend this year’s Graham Jackson Memorial autoimmune regulators through controlled poster prize to include orally presented Congratulations to Sanda Stankovic variation of the mouse genome sequence. papers from the Symposium. It is important who was awarded the Graham Jackson Immunity 2004;20:669-679 that the SIG promote its activities and Memorial Poster Prize. Dorothee Vinuesa C, Cook M, Angelucci C, Athanasopoulos particularly the fact that the SIG provides a Bourges was provided an award as the V, Rui L, Hill K, et al. A RING-type ubiquitin $200 prize for the best Mucosal Immunology runner-up. ligase family member required to repress Poster at the annual ASI meeting. follicular helper T cells and autoimmunity. Nature 2005;435:452-458. Allan W Cripps Dr Kiyono indicated that the 2007 Convenor, SIG Mucosal Immunology Goodnow CC, Sprent J, Fazekas de St. Groth International Mucosal Immunology meeting B, Vinuesa C. Cellular and genetic mechanisms will be held in Tokyo and seeks input from of self tolerance and autoimmunity. Nature ASI Secretariat 2005;435:590-597. the SIG on the style of that meeting. Please PO Box 7108,Upper Ferntree email any suggestions to Ken Beagley (ken. Gully,Vic. 3156 Vinuesa C, Tangye, SG, Moser B, Mackay CR. [email protected]). Nature Rev Immunol. 2005 5:853-865. Australia Tel: +61 3 9756 0128 Ken Beagley briefed the meeting on his Fax: +61 3 9753 6372 activities as the region’s councillor on Email: [email protected] the Council of the Society for Mucosal Offi ce hours: Immunology and indicated that it was 8.30am – 4.30pm 5 ASI Inc. Newsletter June 2006 ASI Councillors’ News

Queensland News attendance by immunologists residing Victorian News several thousand kilometers from Each year the ASI sponsors a prize Queensland’s excentric capital. But it has of student membership for the top become the highlight of our immunology immunology student at the James Cook Following last year’s successful ASI calendar, and achieves an extraordinarily University, which is topped up by JCU with conference in Melbourne, this year’s high level of interest, attracted by both a bookshop voucher. This year the prize conference at the University of Auckland, the caliber of the scientifi c program, as went to Sharne Beatson. Congratulations New Zealand also promises to be an well as the extracurricular activities. also to Queensland ASI member Margaret equally worthwhile event with a number of Last year: polar bears – this year, who Jordan (Comparative Genomics Centre, national and international invited speakers knows? ASI Queensland sponsors awards James Cook University), who received already confi rmed. Details for registration (ASI memberships, medals, and cold the prize for the Best Oral Presentation and abstract submissions can be found at hard cash) for the best postgraduate by a New Investigator at Thymoz 2006 on the ASI web site. http://www.wehi.edu. presentation and the best poster. In Heron Island, April 4-10, 2006. She was au/collegiate/ASI/ addition, ASI members receive a $25 awarded a year’s subscription to Science discount (~10%) on the cost of the by Science editor Stephen Simpson. The next event scheduled for local members meeting. Prof David Hume (Institute is the annual IgV techniques workshop. for Molecular Bioscience, University of This would not be a Queensland News Details of registration, program and Queensland) will feature as this year’s column without mention of Ian Frazer location will soon be available on the IgV Icon (you have to attend the meeting to (director, CICR). He has been awarded website. Another meeting of immunological understand the implications of this), and the Smart State Premier’s Fellowship, interest is the Australasian Vaccines and invited interstate speakers include ASI following his recent Australian of the Immunotherapeutics Development Meeting. President Phil Hodgkin (WEHI), Prof Pat Year award for his work in developing This inaugural meeting will take place in Holt (University of Western Australia), a vaccine for cervical cancer. The the Bio21 Institute, Melbourne from May Dr Carola Vinuesa (John Curtin School fellowship is valued at $1.25 million. 31 to June 1. of Medical Research), and Dr Stephen Turner (Department of Microbiology and This serves as a reminder that the As part of the ASI visiting speaker Immunology, University of Melbourne). extraordinary impact of Australian program, Victoria will be hosting Professor Phil Greenberg’s talk will be another immunology research on health Phil Greenberg on August 7 & 8. Phil is highlight of the meeting, as part of his worldwide well justifi es the increases currently co-director of the Immunology ASI-sponsored tour of Australia as an in medical research funding recently Program of the University of Washington Invited Speaker. Prior to the meeting Phil announced in the Federal budget. Center for AIDS Research and the Head will be visiting the JCU in Townsville. of the Immunology Program at the Fred Finally, announcement of two Hutchinson Cancer Research Center. His Chris Schmidt immunology meetings now open for research interests include the immunobiology Councillor registration: of host T cell responses to infectious viruses and transformed cells and he has pioneered • The Mater Medical Research adoptive transfer of T cells for treatment of Institute’s 8th Annual Dendritic cancer and viral diseases. It is anticipated Cell Symposium will focus on the that Prof Greenberg will visit a couple of topic of Antigen processing, and centres in Melbourne and will be available for this year the keynote speaker is Prof interaction with ASI members. Information Ken Shortman, Walter and Eliza Hall regarding talks and potential interaction Institute. The symposium will be will be emailed to members as they become held on the 13–14 July (http://www. ICB Online Manuscript available. We encourage all members to mmri.mater.org.au/ for up-to-date Submission support this worthwhile program. information). Registration is free, but early enquiries are encouraged. Online manuscript submission for Just another reminder for benefi ts of being Immunology and Cell Biology now an ASI member. This includes eligibility available via: • From August 17–18, the Hotel http://mc.manuscriptcentral.com/icb for a variety of bursaries and awards. There Watermark (Gold Coast) will host are great opportunities for postdocs and this year’s Brisbane Immunology All manuscript submissions to ICB postgraduate students to receive international should in future be made online via this travel awards. There are also travel bursaries Group Retreat (www.qimr.edu.au/big web site to speed up the reviewing and – registration/abstract deadline July acceptance of manuscripts. available for students to attend the annual ASI 14). The BIG Retreat is somewhat meeting. Details concerning awards can be of a misnomer given that it is never Chris Parish, Editor-in-Chief found on the ASI website. held in Brisbane, not to mention the Immunology and Cell Biology Phillip Darcy Councillor 6 ASI Inc. Newsletter June 2006

7 ASI Inc. Newsletter June 2006 2004–2005 Audit Report

8 ASI Inc. Newsletter June 2006

9 ASI Inc. Newsletter June 2006

Hold that date!

The 2006 ASI annual conference will be held in Auckland, New Zealand from December 3–7, 2006.

Invited speakers include Richard Flavell, Marco Colonna, Ian Orme, Bob Coffman and Pam Bjorkman.

More information on the 2006 conference can be found at:

www.asi2006.auckland.ac.nz

10 ASI Inc. Newsletter June 2006

11 ASI Inc. Newsletter June 2006

ASI STUDENT PAGE

It occurred to me when I was looking has emailed you something that you think bucket overnight. at the column from the last issue that is good value, just forward them on to me at the heading was “ASI student page” [email protected]. Amanda Taylor and that maybe I should start thinking about other things to fi ll up a whole Last but by no means least, don’t forget Crossword clues page. I then realised that no way could about the ASI conference at the end of the Across I waffl e on for a whole page so I had to year in Auckland. It’s a great chance to 3 DCs in the skin start thinking about other ways to keep fi nd out what is happening in the world of 5 Location of ASI conference you all entertained that might take up a Immunology down under (and of course 10 Antibody molecules whole page. score a free trip to NZ) and for those of you 11 An abnormal growth getting close to fi nishing, think about all 13 A state of non-responsiveness The result of this is the fi rst ASI student those potential employers. They are so much 14 CD54 crossword and, as I’m sure you can all easier to approach after a few wines at the 15 Forms membrane pores tell, it is the fi rst crossword I have ever conference dinner. 16 A member of the TNF family made. It’s something to keep you busy 17 Small cytokines on those cold winter nights or to burn if Now to leave you, here are a few words that 18 Infection of the blood stream you need a way to keep warm. It’s all don’t exist that should that I got emailed 19 A family of cell surface adhesion based around that subject most dear to a while back. I can’t take any credit for molecules your heart, and no, it’s not about sports, these. 20 A substance that induces mitosis food or the opposite sex. Anything that might seem a bit random will be found Datajinx: The tendency for preliminary data Down somewhere in the newsletter. to become unrepeatable once you’ve told 1 Surname of the NZ council rep your colleagues about it. 2 Programmed cell death If anyone else feels like they have Western splot: Getting high background in 4 Enhances an immune response something to share to give us all a laugh, your Western blot. 6 Failure to response to an antigen feel free to send it to me and if it’s not Eppileft: The single, unused eppendorf tube 7 White blood cells important in parasitic indecent then I will try and include it in that remains after setting up an experiment. infections the next newsletter. (Assuming I don’t Eppilefts are never actually used in 8 Movement of leukocytes through blood get banned after this issue’s crossword experiments; they are typically thrown away vessels attempt). Maybe you have a gift for as contaminated waste. 9 Found in the blood and act together drawing cartoons or even if someone Floaters: The tubes you forgot in the ice 11 Site of T cell development 12 Genetically identical except at one loci

12 ASI Inc. Newsletter June 2006 ASI Annual Meeting: “Immunology – From Bench to Bedside” Auckland, December 3–7, 2006

The ASI annual conference will be held in abstracts. When registering, please signify Immunology in 1992 from the University Auckland, New Zealand and we’re delighted that you wish to be eligible for the Young of Oxford. He sub-sequently spent 5½ to invite you all to what will be a meeting Investigators Award. years as a postdoctoral fellow at the that again celebrates all that is exciting National Institutes of Health, USA. In about Immunology and its applications. The Accommodation 1998, he joined the Imperial Cancer meeting will be held in the newly constructed We offer a five star hotel, Langhams, Research Fund, now Cancer Research Engineering complex on Symonds Street, in located at the top of Symonds Street. UK London Research Institute, as head the heart of Auckland University and very Rooms at Langhams are $180/night. A of the Immunobiology Laboratory. close to downtown Auckland, hotels and mid-priced hotel, Quest on Mount, offers He is currently a Principal Scientist university accommodation. If you have not a slightly cheaper alternative, and budget and holds honorary appointments at been to Auckland, this is a golden opportunity accommodation has been organised at University College London and Queen to experience Auckland hospitality and O’Rorke Halls of Residence at $55/night. Mary, London. His research centres on combine some excellent science with a great Each is within easy walking distance to the regulation of adaptive immunity social programme. the meeting. Contact details for hotels are by antigen-presenting cells and innate available on the website. recognition mechanisms leading to The theme of the 2006 meeting is “From immune activation. Bench to Bedside” stressing the importance Invited speakers of applying basic immunology to resolving Professor Richard Dr Marco Colonna clinical problems. Our Burnett orator has Flavell (Yale (Washington been chosen carefully with this theme in University) University) mind. Professor Marc Feldman, an Australian Prof. Flavell is Sterling Marco Colonna now domiciled in London, is best known for Professor of Immuno- obtained his MD his work in developing anti-TNF reagents biology at Yale University degree from the that are now widely used in the treatment of School of Medicine, and School of Medicine, rheumatoid arthritis and other infl ammatory an Investigator of the University of Parma diseases. Professor Feldman was the 2003 Howard Hughes Medical and completed post- recipient of the Albert Lasker Prize in Institute. He received his BSc (Honors) doctoral training Medicine for his contribution to the treatment in 1967 and PhD in 1979 in biochemistry at the National of rheumatoid arthritis. from the University of Hull, England, and Cancer Institute of Genova, Roswell performed postdoctoral work in Amsterdam Park Memorial Institute, and Harvard We have a superb line-up of international (1970–72) and Zurich (1972–73). Before University. He established an independent speakers covering the spectrum of current accepting his current position in 1988, Prof. laboratory at the Basel Institute for immunology (see below). In addition, 24 Flavell was fi rst Assistant Professor at the Immunology in 1994 and was appointed separate symposia that cover the usual themes University of Amsterdam (1974–79); then Professor of Pathology, Immunology and of Immunology are planned throughout the Head of the Laboratory of Gene Structure Medicine at the Washington University four days. A special symposium/workshop and Expression at the National Institute School of Medicine in St Louis, MO, in is planned this year on Immunology for Medical Research, Mill Hill, London 2001. He focuses on receptors mediating teaching. (1979–82); and subsequently President and innate immune responses, a fi eld in Chief Scientifi c Offi cer of Biogen Research which his accomplishments include Specialist workshops Corporation, Cambridge, Massachusetts identifi cation and characterization of the The Tumour Immunology and postgraduate (1982–88). Prof. Flavell is a Fellow of the Killer cell Ig-like receptors and HLA- training workshop will be held on Sunday Royal Society and a member of the National C polymorphisms as their inhibitory 3rd before the opening of the meeting. As Academy of Sciences. Richard Flavell uses ligands, as well as discovering the LILR usual, separate registration for TIW and the transgenic and gene-targeted mice to study T and TREM inhibitory and activating postgraduate workshop is required. cell tolerance and activation in immunity and receptor families. autoimmunity, apoptosis, and regulation of T Registration cell differentiation. Dr Ian Orme All registrations will be conducted on-line. (Colorado State The web-site, www.asi2006.auckland.ac.nz, Dr Caetano Reis e University) will be accepting registrations from around Sousa (London Ian Orme is Professor the middle of May. Research Institute) of Microbiology, Caetano Reis e Sousa Immunology Young Investigator Award obtained a BSc(Hons) and Pathology at This will be offered again in 2006 and fi nalists in Biology in 1989 Colorado State will be selected by a panel from submitted from Imperial College, University in Fort London, and a DPhil in 13 ASI Inc. Newsletter June 2006

Collins, Colorado. He worked as a twenty years. He obtained his PhD at the parallel mechanism for the regulation of IgA technician in the Immunology Department University of Cape Town, South Africa. He responses by Transforming Growth Factor- at the Institute of Child Health in London completed a postdoctoral fellowship at The beta. Over the past decade, Dr Coffman’s before attending the University of London Rockefeller University in the laboratory of laboratory has studied the functions of T where he graduated in 1977 with a First Dr Zanvil Cohn. Dr Aderem rose through cell regulation a number of immunological Class Honors degree in Physiology. the ranks at The Rockefeller University, diseases. These include studies of asthma He then worked in the Immunobiology becoming head of the laboratory of Signal and allergic disease mechanisms, the Department at Burroughs Wellcome Transduction in 1991. In 1996, he accepted genetic basis for differences in Th1 or Th2 while studying for an external PhD degree a professor of Immunology and Medicine responsiveness, and the importance of Th1 in Immunology, which was awarded in position at the University of Washington in cells in causing and regulatory CD4+ T 1981. From 1981–1986 he did his post- Seattle. In 2000, Dr Aderem co-founded the cells in preventing infl ammatory bowel doctoral training at the Trudeau Institute, Institute for Systems Biology (ISB) with Drs disease. In addition, his laboratory has made Saranac Lake, New York State under Leroy Hood and Ruedi Aebersold. The ISB important contributions to understanding the supervision of Dr Frank Collins. He is an interdisciplinary institute that focuses the role of T cell and cytokine responses in joined the faculty at CSU in 1986 and on global analysis of complex systems determining the form and severity of several was promoted to Professor in 1995. He including the immune system. Dr Aderem tropical parasitic diseases. Dr Coffman has has published over 230 publications on has been the editor of several journals authored over 200 scientifi c publications. the immunology of tuberculosis in the including the Journal of Experimental In 1997, he received the William S. Coley mouse and guinea pig models. He has Medicine. He has also organized a number Award for research in Basic and Clinical been the recipient of multiple awards, of scientifi c meetings including the Gordon Immunology. including the Roussell prize, the Charles and Keystone Conference on immunology H. Shepard award, and the CSU Scholar and systems biology. He was a Pew Scholar Professor Pamela Impact Award. In 2002 he was elected in the Biomedical Sciences and has a MERIT Bjorkman (California Fellow of the American Academy of Award from NIAID. Dr Aderem has a Institute of Technology) Microbiology. longstanding interest in developing world Professor Pamela J. medicine. He serves as a science advisor to Bjorkman is the Max Professor Steve the South African government and chaired Delbrück Professor of Henry (Auckland a Parliamentary Review Commission of the Biology and an HHMI University of South African Medical Research Council in investigator at the Technology) 1996 and 2001. California Institute of Technology and Professor Steve Adjunct Professor of Bio-chemistry at the Henry is the Chief Dr Bob Coffman University of Southern California School Executive of the (Dynavax, Berkeley) of Medicine, Los Angeles. She received a Auckland University Dr Robert L Coffman is BA degree in chemistry from the University of Technology the Vice President and of Oregon and a PhD in biochemistry from Biotechnology Chief Scientifi c Offi cer Harvard University. As a graduate student Research Institute of Dynavax Technologies and postdoctoral fellow in Don Wiley’s and is the founder and CEO of the in Berkeley, CA. Prior laboratory, she solved the crystal structure biotechnology company Kiwi Ingenuity to joining Dynavax in of a human histo-compatibility molecule. Limited. Steve leads a team of 16 2000, Dr Coffman was She continued her postdoctoral training at biotechnology researchers focusing on a founding member of Stanford with Mark Davis, where she worked commercially viable cell surface the Scientifi c Staff of the DNAX Research on T cell receptors. Prof. Bjorkman is a modification/manipulation (KODE Institute in Palo Alto, CA. He has devoted member of the National Academy of Sciences technology) of cell surfaces. Steve the past 20 years to unravelling the pathways and the American Philosophical Society. She originally trained as a medical laboratory of immune regulation by T cells and has received the William B. Coley Award scientist specializing in transfusion cytokines. In 1985, Dr Coffman discovered for Distinguished Research in Fundamental medicine and later completed PhDs that Interleukin-4 and Interferon-gamma Immunology from the Cancer Research in biochemistry and transplantation were the principal cytokines regulating Institute (shared with Don C. Wiley and Jack medicine. He has published over IgE production in allergic responses. In L. Strominger), the James R. Klinenberg 100 scientific papers, abstracts and 1986, with colleague Dr Tim Mosmann, Science Award from the Arthritis Foundation, international patent applications. he defi ned the two principal subtypes of the Gairdner Foundation International helper T cells, termed Th1 and Th2 cells, Award for achievements in medical science Dr Alan Aderem and demonstrated subsequently that the (shared with Don C. Wiley), and the Paul (Institute of Systems three major features of allergic responses, Ehrlich and Ludwig Darmstaedter Award Biology, Seattle) IgE, eosinophilia and mast cell hyperplasia, (shared with Jack. L. Strominger and Hans- Alan Aderem has were co-ordinately regulated by the Th2 Georg Rammensee). Prof. Bjorkman’s studied the interface subset of T cells. Dr Coffman demonstrated laboratory is interested in protein-protein between the innate that Interleukin-4 mediated class switching interactions, particularly those mediating and adaptive immune to IgE by controlling rearrangement of immune recognition. The laboratory uses system for more than immunoglobulin genes and discovered the X-ray crystallography and biochemistry to

14 ASI Inc. Newsletter June 2006 study purifi ed proteins, and is beginning to his clinical training and to pursue studies in Professor Marc Feldman (Imperial include confocal and electron microscopy viral immunology and autoimmunity at the College London) – Burnett Orator (EM) to examine protein complexes in cells. Walter and Eliza Hall Institute of Medical 2006 Some of the work focuses upon homologs Research with Prof. Ian Mackay. In 1985 and mimics of class I MHC proteins. These he moved to Brisbane to take up a teaching proteins have similar three-dimensional post with the University of Queensland, and structures, but different functions including he now holds a personal chair as head of the immune functions (IgG transport by the Centre. His current research interests include neonatal Fc receptor, FcRn; evasion of the immunoregulation, and immunotherapeutic immune response by viral MHC mimics), and vaccines for Papillomavirus associated non-immune functions (regulation of iron or cancers, for which he holds research funding lipid metabolism by HFE and ZAG). Prof. from several Australian and US funding Bjorkman’s laboratory is also comparing the bodies. Dr Frazer teaches immunology to structures and functions of host and viral Fc undergraduate and graduate students of receptors with FcRn. the University. He is on the board of and chairs the Medical and Scientifi c advisory Dr Thomas committee of the Queensland Cancer Fund. Blankenstein (Berlin) He is vice president of the Cancer Council Professor Feldmann is the Head of the Thomas Blankenstein Australia. Kennedy Institute of Rheumatology received his PhD from the Division, Faculty of Medicine, Imperial Institute of Immunology Associate Professor College London. He gained his MBBS in Cologne, Germany. He Fabienne Mackay (1967), BSc Med (Hons) (1970) and PhD analyzed the molecular (Sydney) at the Walter & Eliza Hall Institute (with evolution of immuno- A/Prof Mackay obtained Sir Gus Nossal), all at the University of globulin variable region her PhD in 1994 at the Melbourne (Australia) (1972). He went genes such as gene duplications, gene Louis Pasteur University to London in 1972 to take up postdoctoral conversion and genomic organization. in Strasbourg. Co- position with Professor N.A. Mitchison Since 1988 when he joined the Institute supervision: Dr Werner at the Institute of Cancer Research of Immunology of the Free University of Lesslauer (Hoffmann La Roche, Basel Fund, University College Hospital (now Berlin, he worked in the fi eld of cancer Switzer-land) and Prof. Diane Mathis. In Cancer Research UK) where he gained a immunology. He analyzed whether and 1994, A/Prof Mackay joined BiogenIdec permanent senior staff position in 1974. under which conditions cytokines contribute Inc in Boston where she dissected the role He joined the Sunley Research Centre to tumor rejection. Currently, he is group of lymphotoxin-alpha/beta in autoimmunity in 1985 as the Deputy Director and leader at the Max-Delbrueck-Center for and cancer. This work led to many patents Head of the Immunology Unit, which Molecular Medicine (since 1994) and head and the development of two new treatments amalgamated with the Kennedy Institute of the Institute of Immunology of the Charite, currently tested in the clinic. In 1998, A/Prof of Rheumatology in 1992 and from then Berlin (since 2000). Some discoveries over Mackay’s lab cloned a new member of the until 2002 he was the Deputy Head of the last 5-10 years are: (1) B cells inhibit the TNF family, named BAFF, and discovered Division and Head of Cytokine Biology generation of tumor immunity; (2) The tumor the role of this new molecule in B cell-driven and Cellular Immunology Department. stroma is a critical target for tumor rejection autoimmunity. In 2000, A/Prof Mackay His chief interest is the molecular by T cells; (3) IFN-γ inhibits tumor-induced joined the Garvan Institute in Sydney as a pathogenesis of inflammatory and angiogenesis; (4) Tumors do not lose their Welcome Trust senior research fellow and rheumatic disease, with a special interest intrinsic immunogenicity, while growing was awarded a NHMRC program grant. A/ in the role of cytokines in rheumatoid in immune-competent hosts. Further work Prof Mackay’s lab at Garvan discovered the arthritis. His major accomplishment has is on T cell engineering for more effective role of BAFF as a key B cell survival factor been to discover the important role of adoptive T cell therapy. essential for the maturation of B-lymphocytes TNFa in the pathogenesis of rheumatoid and became one the leading group on BAFF arthritis; this has led to the award, jointly Professor Ian Frazer research. In March 2006, A/Prof Mackay with Professor Sir Ravinder Maini, of (Queensland) was appointed to director of a research unit the Crafoord Prize of the Royal Swedish Ian Frazer is Director on Autoimmunity. Her unit has a program Academy of Sciences in 2000 and the of the Centre for studying BAFF, the role of B cell subsets Albert Lasker Clinical Medical Research Immunology and Cancer in autoimmunity and neuro-immunology Award in 2003 for the discovery of anti- Research, a research projects studying the role of stress hormones TNF therapy as an effective treatment centre of the University on immune functions. A/Prof Mackay has for rheumatoid arthritis and other of Queensland at the authored more than 40 articles/reviews/book autoimmune diseases. Princess Alexandra chapters, many in high impact factor journal Hospital in Brisbane. He was trained as a journals and she is a consultant for several renal physician and clinical immunologist biotech and pharmaceutical groups. in Edinburgh, Scotland before emigrating in 1981 to Melbourne, Australia to continue

15 ASI Inc. Newsletter June 2006

Comments on ASI from Members

On the Membership Information Update form which accompanies the membership Yes – active state committees, good ASI is well organised and doing a great renewal, members are asked to comment conferences, good newsletters. job. on whether ASI meets the member’s Mostly – not enough visiting speakers Very happy. expectations for a Scientifi c Society. coming to NZ! ASI is excellent. This year, a total of 46 comments were It would be great to have more ASI training/ received from the 591 who had renewed I think member services for students are seminars in the area of Education – University at the time of preparing this newsletter. limited. ASM provides grants for students to level immunology - share ideas, etc. Of these, 23 simply said either Yes or travel interstate to learn about new techniques Meets my expectations, or variations I think ASI does a fi ne job with conferences, and fosters inter-lab collaboration better. on that theme. The more substantive workshops and keeping us up to date on I am enjoying my time as a Student comments are listed below: relevant news through the newsletter. Representative and also ASI has been I would like to see some more emphasis on valuable in organizing conferences and Doing well – 2005 meeting a great Veterinary Immunology. workshops. success More student bursaries for travel to overseas Really great society! Wouldn’t change it. I would like to see publication of the conferences. annual ASI meeting abstracts – if not in ASI has met all of my expectations. Great Immunology & Cell Biology, then at least Yes, I am satisfi ed with the services ASI work. as a member-accessible PDF. provides me. ASI does meet my expectations. I can’t think Yes. Good job done by many willing and ASI 2005 was a fantastic conference. of anything that may help to improve it. friendly volunteers. I appreciate the regular emails which keep us The scientifi c meeting in Melbourne in up-to-date on seminars and visiting lecturers 2005 was excellent. etc. Annual conferences are always well organised and worthwhile, newsletter is More attention to clinical immunology informative, therefore meets expectations. is urgently required. Yes, I think ASI does a good job.

16 ASI Inc. Newsletter June 2006

An Immunological Saga Tony Basten Professor Tony Basten retired as Director of the Centenary Institute earlier this year. Here he refl ects upon a career in Immunology.

Early Years: 1958 the animal reservoirs, but the standard form to my horror I found the name Krebs, My fi rst inkling that there was a subject of suicide amongst Eskimos was ingestion H with citations going on for pages. called immunology occurred in 1961 when of uncooked polar bear meat. Six months ‘When you have as many citations as I I was in fourth year medicine at Adelaide later, however, I was still standing, albeit have young man, you may piss into my University – my fi rst teacher the newly intoxicated with ether and the rats had Nobel equipment as much as you please, appointed Professor Derrick Rowley. The developed a substantial eosinophilia. but until then get out!’ A week later he most vivid recollection I have of him was invited me back to use his equipment his vintage blue Austin Seven which one day The next step was to isolate the eosinophilic instead under Bill’s guidance. we took to pieces and re-assembled in his factor from the parasite for which I was offi ce in the lunch hour. Although this was instructed to use a high voltage water It was about this time in 1967 that a sore test for his Yorkshire temperament, cooled electrophoresis ‘machine’. The lymphocytes were becoming fashionable he gracefully allowed the culprits, after instruction manual (dating back some 20 and the discoverer of their functional exhaustively researching our identities, to years) recommended running the machine capabilities, Professor Jim Gowans, was pass at the end of the year. over the weekend. This I did, but on Monday just down the road in the Dunn School morning when I arrived in the lab I was met where Florey had developed penicillin My one foray into research during my by a very short, very irate man whom I did as a therapeutic. I told him that I had a undergraduate days was in the department not recognise. He took me, protesting, by bee in my bonnet that eosinophilia was of surgery where I measured sodium levels the ear and conducted me downstairs to a T cell dependent and asked him to teach by fl ame photometry in bile collected from lab which was fl ooded with water from the me thoracic duct cannulation. Not only patients undergoing T-tube drainage post machine and contained a brand new gamma did he do so, but met me in his lab every cholecystectomy – a far cry from immunology counter. From this was emerging roll upon night to collect the lymph. Thanks to him but a paper (my fi rst) nevertheless in a roll of printout containing nothing but the I was able to prove the hypothesis and journal, albeit with an unrecorded impact words ‘you dill Bill, you dill Bill …’ – Bill be awarded my D.Phil. The doctorate factor. being the name of the chief technician as was presented in Christopher Wren’s I gathered later. Being human I laughed, Sheldonian Theatre by Sir Peter Medawar The Oxford Years: 1966 – 1969 another serious mistake, and was then taken who gave the occasional address in Latin My real career in Immunology began into this man’s offi ce. After taking down and then in English. How fortunate I was serendipitously when I arrived in Oxford on a the Index Medicus, he asked me my name: that Witts had retired, presenting me with Nuffi eld Clinical Assistantship in early 1966 ‘Basten, A, sir’. Under that name he found the opportunity to interact with such a just a few months after the new professor six citations. Having handed me the tome, stellar group of scientists and become an of Medicine, Sir Paul Beeson. In contrast to I was invited to turn to page 205 where immunologist not a haematologist. his haematological predecessor, Witts, with whom I was originally supposed to work, Beeson was one of America’s renowned experts in infectious disease who by chance had previously collaborated with Derrick Rowley on the role of complement in renal disease – a small world indeed. He offered me two projects, one to study the effects of iodides on granulomas and the other on the mechanism of eosinophilia which appealed rather more. One reason for this was the fascination the eosinophil had held for many a scientist in the past. Thus by 1914 there were 2758 references in the literature compared to a few hundred for neutrophils and a handful for macrophages. As a greenhorn in the lab, I was set to work grinding up rat muscle to yield the parasite Trichinella Spiralis as a stimulus for eosinophilia. On reading about it, I discovered with some concern that not Tony Basten (left) with a young Mark Hogarth and Bob Raison only were polar bears, pigs and stray cats at 1980 World Congress in Japan 17 ASI Inc. Newsletter June 2006

immunological horizon. In the Miller Unit exceptionally strong thanks to Ruthven Then followed a year of uncertainty. I the focus was on the latter and we established Blackburn, whereas there were great was due to do my postdoc with John them as a fail safe mechanism in tolerance opportunities to develop research oriented Humphrey at the National Institute of just after Peter McCullagh at ANU and units. My fi rst lab was located in David Medical Research in London’s Mill Hill Dick Gershon in USA published the initial Nelson’s section of de Burgh’s department. (where James Murray began his famous reports on their existence. Our suppressor My offi ce had the unique feature of being work on the Oxford English Dictionary). cells were CD 8+ as well as expressing the the preferred location for the largest and Humphrey, however, regularly smoked a elusive MHC related IJ molecule.T cell most sluggish blow flies in Australia. pipe in his offi ce and after falling asleep, derived soluble factors were the province of Nevertheless it was possible to work on burnt half his laboratory down. He and Marc Feldmann, then a PhD student in the suppression in tolerance and immunity and Gowans then put their heads together. Nossal Unit and my squash partner. By using to add the now forgotten Transfer Factor Their solution was to put me in touch the then famous Diener/Marbrook double (TF) to the menu. This low molecular with Jaq Miller at the Walter and Eliza chamber culture vessel we demonstrated weight leucocyte extract according to New Hall Institute and what a great solution the existence of antigen specifi c and non- Yorker, Sherwood Lawrence could transfer that turned out to be. specifi c factors by placing T cells above DTH to naïve recipients. In the absence of and B cells below what we believed to be a T cell receptor or any known cytokines, WEHI years: 1970 – 1972 a cell impermeable membrane. Some years this intrigued a number of immunologists, I recall appearing for the fi rst time in later it was shown that T cells could in fact among them a student of James Watson who Jaq’s lab when he was doing neonatal migrate through the membrane but Marc fraudulently claimed that TF contained low thymectomies with a technician who had had moved on and begun his seminal work molecular weight mRNA-a cause celebre the miniest of mini skirts. On my arrival on the role of TNF in infl ammation which at the time. In collaboration with Chris in the lab he asked ‘Who are you?’ he formed the basis of his and Tiny Maini’s Parish, we subsequently showed it in fact asked and when I replied he said, ‘Oh use of anti-TNF monoclonals in treatment contained fragments of antigen and low good, come back in six weeks – I am of rheumatoid arthritis. molecular weight Ia, thereby explaining its busy’. Fortune favoured me again and I apparent specifi city. On the other hand, TF found solace next door with Jon Sprent This era completed my training and the was side effect free and we used it to treat who had 30 mice cannulated on old jam acquisition of an array (range) of wonderful immunodefi cient patients, including those tins and with whom I have remained fi rm colleagues and mentors who have continued with APECED, with anecdotal success as friends ever since. to enrich my career. It was at this time that well as conducting a two year controlled I was greatly buoyed by coming across trial in multiple sclerosis where patients In those days, WEHI under Gus Nossal’s Burnet’s wittiest aphorism. In answering the with relapsing disease appeared to benefi t directorship was amongst the most question of why support research, he wrote: due, it seemed, to a reduction in the number exciting and dynamic immunological ‘Rulers of any ideology have always found of febrile episodes and consequent relapses. centres anywhere in the world. Even it dangerous to have a considerable group of TF has now sunk into obscurity and unlike for young scientists there were so many unemployed intellectuals and professionally suppressor cells has not been resurrected. experiments just waiting to be done. trained men’. Ironically, however, it did more to promote Jon and I thought we would solve our image in the community than all our immunological memory by determining /Royal Prince Alfred Nature papers put together! whether it was a quantitative or qualitative Hospital era: 1972 – 1982 phenomenon. The primed mice yielded When my Fellowship at the Hall Institute During the late 70s, T cell dependent 20% antigen binding cells in thoracic fi nished, I had three options: to stay on as suppression remained in vogue and was duct lymph versus < 1% in controls Jaq’s second in command, to apply for a widely accepted by the immunological – QED I thought but was unable to repeat senior lectureship at Sydney University in the community to the extent that it was a the experiment. Eventually the penny departments of Bacteriology and Medicine guaranteed ticket to Brook Lodge and Cold dropped: the primed mice of course had with Professor Pat de Burgh (the BSc. Med. Spring Harbor Symposia. The 1976 CSH made antibodies which adhered loosely Supervisor of Metcalf, Nossal and Miller) and symposium was particularly memorable to Fc receptors on the B cells and could Professor Ruthven Blackburn respectively, with suppression being interwoven with the be washed off before addition of antigen or to accept an offer from Derek Rowley to discovery of MHC restriction by Doherty but not afterwards. The moral: always put return to Adelaide. The latter proposal was and Zinkernagel. While our host, JW, was the number of centrifugations in one’s day most fl attering as Rowley informed me that selecting his postdoc for the night, Peter book. The discovery of the Fc receptor I had improved signifi cantly since my days Doherty was standing on the table setting was therefore pure luck or serendipity. as a rather ‘mischievous’ undergraduate. The up a new research centre. My appointed A bonus for me was working with Noel problem, however, was that I would have to task was to act as the medical offi cer since Warner (now a Vice President and head of fi nd a salary – no easier then than it is now! suppression, in his view, was ‘a load of old R&D at BD) to establish the heavy chain Although a hard decision at the time to pick cobblers’. What led to its temporary demise binding specifi city of the FcR. between Sydney and Melbourne, I decided on was the failure to identify a gene for IJ and Sydney, a choice I have never regretted. development of impossibly complex circuits The early 70s was also the time when linked by suppressor factors which existed T cell derived soluble factors and Sydney in those days was very different only in vitro. Now suppressor cells have been suppressor T cells fi rst emerged on the from Melbourne: clinical medicine was reinvented as Tregs and the old literature

18 ASI Inc. Newsletter June 2006 conveniently forgotten. and the HEL/anti-HEL pizza eating mice cheek by jowl with behavioural scientists were born. The choice of B cells not T and epidemiologists and; (b) the fact that At the same time I was tasked with the cells to study was a tactical masterstroke of AIDS had been taken off its artifi cial responsibility of setting up a clinical the type for which Chris has now become pedestal and reinstated into mainstream immunology service at nearby Royal Prince famous. He worked in close association with medicine – very much to the benefi t of Alfred Hospital. In those halcyon days all Jeff Crosbie and Rob Brink, both of whom the patients. On the negative side was the one had to do was write a one page letter to remained part of the home team while Chris stultifying effect on decision making of the hospital General Superintendent and a has gone on to achieve great things, fi rst at the bureaucracy and army of government secretary followed by two scientifi c offi cers Stanford and more recently at the John Curtin consultants. Nevertheless the fi rst White materialised. The next 8–10 years were School in Canberra. To be part of the early Paper on AIDS was a credit to this country among the happiest of my professional life days of transgenic models was for me an and the disease has continued to be because at that time it was still possible to absolute delight and real compensation for managed sensibly ever since. combine competitive basic research with the drudgery of administration. The editor of clinical medicine. I was privileged to work this Newsletter will remember the CIRCUS Centenary Years: 1989 – 2005 alongside a cadre of great physicians and when he worked there as a BSc Med student The origins and early history of the resident staff the fi rst two of whom were with a square foot of bench space and a place Centenary Institute of Cancer Medicine Graeme Stewart and Paul Gatenby, now of on the conduit for the tie he never wore. and Cell Biology are summarised in a course distinguished in their own right. Rarely 1999 paper published in the Medical did a week go by without an immunological HIV AIDS Years: 1987 – 1989 Journal of Australia. In practical terms case being presented at Grand Rounds: ‘if Early in 1987 I received an unexpected phone it is one of the second generation of the cause of a disease was unknown then call from the then Federal Health Minister, independent institutes originally created it must be immunological’– a view which Neal Blewett, inviting me to take over the around the CIRCUS in the image of the was very good for our image! Because of its Chairmanship of the AIDS Task Force with major Melbourne institutes, the goal being intrinsic importance in pathogenesis of many Ian Gust, the Founding Director of the to co-ordinate research in NSW, to act as diseases, immunology became a recognised Burnet Institute as Deputy. This proved to a beacon for attracting back from overseas specialty in the Colleges of Physicians and be a fascinating challenge as HIV/AIDS and outstanding young Australian scientists Pathologists in 1974 with the fi rst training its management were still in their infancy. and to obtain block grant funding from the centres in Sydney being located at Royal I came to meet and work with not just the NHMRC. Since its creation, Centenary Prince Alfred and St Vincent’s Hospitals Bruce Shepherds of this world, but the gay has been best known for its immunology, under the direction of myself and Ron community, IV drug users, the Prostitutes although in recent times outstanding Penny respectively. Consequently our unit Collective – all much better educated about molecular biologists like John Rasko, became a focus for combined clinical and the disease than the population at large and Chris Semsarian and John Allen have research training for those aspiring to be other groups like the Breast Feeding Mothers joined the staff and expanded the research immunologists/allergists per se and aspirants Association. The latter in a sense epitomised base. Thanks to the magnifi cent efforts from the many other related disciplines. When the issues raised by AIDS, their stance at the of the management team, particularly trying to seduce PhD students to join the lab, time being that pregnant women should not Denyse Bartimote (General Manager) I always enjoyed quoting Peter Medawar’s be tested for the virus which to me implied and Jeff Crosbie (Operations Manager), defi nition of clinical immunology: ‘It bears that the unborn had no rights. The Task as well as key members of the Board like upon every branch of medicine and every Force was subsumed into the Australian Dr Bernie Amos (then Director General organ system in the body.’ National Council on AIDS (ANCA). The of State Health), we secured the 21 new council was chaired by Professor Peter million dollars needed to commission The CIRCUS: 1982 – 1989 Karmel, formerly chairman of the AUC, a a new building which was offi cially 1982 was the year when the immunology unit distinguished economist and father of seven opened by John Howard in 1997. The became the Clinical Immunology Research with Ron Penny and myself as the Chief opening ceremony was a great success Centre University of Sydney (known as Advisers on Education and Medical and despite being overshadowed by Pat Rafter the CIRCUS), one of the fi rst 10 Centres Scientifi c Aspects of AIDS respectively. winning the US Tennis Open just as the of Excellence to be set up by the Federal PM took to the podium. Government. The Medical School could Fronting up to the media as one of the ‘three not accommodate us so that we moved wise monkeys’ (a Karmel term) was quite What was the highlight for me during into a picturesque 19th century ‘classic’ an experience, but we had good backup my 15 years as Director was the number building which was formerly the morgue, since ANCA contained some of Australia’s of talented young men and women who the residents’ quarters and Dermatology top research brass including not just Ian chose to work at Centenary and on whose ward before being declared uninhabitable Gust but Fiona Stanley, Peter McDonald performance its track record is now fi rmly by patients (but not by immunologists). and John Chalmers. At my interview with based. In addition, Centenary of today The building was shared with the hospital the press on my resignation to become the has one of the best fl ow cytometry and department with which close ties have existed Centenary’s Director, I recall making three transgenic animal facilities in the country ever since. points. On the positive side of the equation as well as a diversifi ed research staff were: (a) the creation of the fi rst multi- which augurs well for the future be it in As suppression waned, transgenesis was disciplinary grants committee (CARG) immunology, cancer or some other fi eld. introduced to the centre by Chris Goodnow where virologists and immunologists sat The challenge for the new director will as

19 ASI Inc. Newsletter June 2006

of Burnet, Lafferty, Miller and Nossal is alive and well. What was particularly impressive was the depth and variety of the scientifi c presentations. In addition to those of the usual high fl iers, there were a number of outstanding presentations from students, postdocs and research fellows. To try and keep up with these young stars, I plan to spend 6–12 months at the Laboratory of Molecular Biology in Cambridge brushing up on my pipetting, annealing and thinking with Greg Winter, Michael Neuberger and Doug Fearon. The real challenge, however, for an ex Oxford man will be punting from the wrong end of the boat!

I do sometimes wonder what is the long term future for immunology and its tool box of vaccines, cytokines and monoclonals. The more effective these tools become, the Tony Basten with Prime Minister Howard and Professor Peter Doherty AC at more likely is it that the burden of infectious offi cial opening of new building in 1997 (you can see we are celebrating Pat Rafter's disease and cancer will diminish – will the victory) world cope with the resultant increase in population? Being a born optimist I think it will. I agree with Gus Nossal’s view always be to secure the resources needed Chris Parish and Geoff Shellam, the former a of immunology expressed as long ago as to preserve what is a very valuable asset wonderfully stimulating ideas and techniques 1982: ‘The overwhelming impression is one for NSW and Australia. man as well as a pioneer in biotechnology of tremendous growth in knowledge and and the latter a great contributor to NHMRC power; of a discipline that has reached full Colleagues and Friends and the Fellowships’ scheme over the years. maturity and independence; of a future with Personal friendships are one of the Finally I have been greatly privileged to be possibilities.’ bonuses of doing research, often associated at the CIRCUS and Centenary overlooked in a life of grant deadlines, with many talented students and colleagues meetings and student responsibilities. like Barbara Fazekas, Chris Goodnow and I have already mentioned some of the Phil Hodgkin, all of whom have excelled in senior immunologists responsible for their own right. Indeed, 16 of them now head UPCOMING shaping my career particularly Jacques their own research enterprises or departments CONFERENCES Miller who, in my book, is as multi- and even faculties across Australia. By way talented as the likes of Edward Jenner. The of acknowledgement I would be so bold as 17th Annual Meeting – ASCIA latter, in addition to pioneering smallpox to quote from Isaac Newton: ‘If I have seen September 7–10, 2006 vaccination, was an oboist, ornithologist further on occasions, it is by standing on the Sydney and curator of the British Museum, while shoulders of giants’. incorporating ASCIA Primary Care Jaq is not just the discoverer of the thymus Allergy & Immunology Update, but an accomplished artist, French chef In Peter Doherty’s eminently readable book September 10 and an authority on Dante’s Inferno. entitled ‘The Beginners Guide to Winning Website: www.allergy.org.au However, it is also timely to acknowledge the Nobel Prize’, he lays down 18 criteria for the friendship and support of my peers. being a successful scientist. On running my International Conference of Jon Sprent, Peter Doherty and Marc career past them, I score well for choosing Immunogenomics and Immunomics Feldmann have been life long colleagues an appropriate fi eld (Immunology!), working October 8–12, 2006 and a source of many stimulating hours with the right people, being prepared to Budapest, Hungary of discourse on virtually every topic fail and enjoying my fair share of luck. On Website: www.bcii2006.org known to man. Likewise the 2005 Burnet the other hand, I have done less well in my Orator, Ian McKenzie, whose generosity attempts to avoid what he termed ‘prestigious 3rd International Congress on Healthy with reagents in the early days of the two administrative roles’ and being a dilettante, Ageing and Longevity cell system is legendary, his successor i.e. working on both T and B cells. October 13–15, 2006 at the Austin Research Institute, Mark Melbourne Hogarth who has made the FcR his own, The Future Website: http://www.longevity- and Mauro Sandrin whose expertise at Having attended the 2005 ASI meeting international.com/ snooker improves exponentially after in Melbourne, I can say without fear of midnight. A little farther afi eld have been contradiction that the immunological legacy

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