PROFESSOR PETER MICHAEL WATERHOUSE, FAA Current appointments  Federation Fellow, University of Sydney Joint appointment between School of Biological Science and School of Molecular Biosciences  Honorary Fellow, CSIRO – Plant Industry, Canberra, Australia

Employment history: 1978-79 University of Cambridge, England. 1979-82 PhD. Student, Scottish Crop Research Institute, Scotland. 1982-2008 Research Officer –> Chief Research Officer, CSIRO Plant Industry, Australia. 1992-3 Visiting Fellow, MRC / University of Cambridge/ CAT Ltd, England 1997-9 Program Leader, CRC for Plant Sciences, CSIRO/ANU, Canberra, Australia. 2008- Federation Fellow, University of Sydney, Australia.

Recent Awards 2002 Victor Chang Medal. 2003 The Bulletin: Smart 100: Science – Top Ten Finalist. 2003 IMTC-ISI/Thomson “Most Highly Cited in Field” Award. 2005 CSIRO Chairman’s Medal. 2007 The Bulletin: Smart 100: Science -Top Ten - Winner. 2007 ARC Federation Fellowship. 2007 Prime Minister’s Prize for Science. 2009 Fellow of Australian Academy of Science.

Scientific Advisory, Editorial, or Review Boards Prime Minister's Science Council (Keating, 1995) Prime Minister's Science, Engineering and Innovation Council (Howard, 2007) Prime Minister's Science, Engineering and Innovation Council (Rudd, 2008) SAB: Nemgenix Pty, Australia (2008-) Ed. Plant Methods http://www.plantmethods.com/ (2004- ) Ed. Molecular Plant Pathology (Wiley-Blackwell, 2003-8) Ed. Functional Plant Biology (CSIRO Publishing, 2004-9), Ed. Silence (BMC, 2009- ) Review Board for Scottish Crop Research Institute, Genetics Program (2009)

Competitive Grants: ARC FF, Discovery & Linkage/Industry/CSIRO-external, since 2008 : ~ $5M

Patent Portfolio (Named Inventor)  A suite of 11 families of patents (granted/in contest/provisional) on RNAi (CSIRO and Bayer)  Two granted patents on recombinant antibodies (MRC and Cambridge Antibody Technology Ltd)  One granted patent on virus resistant plants (CSIRO and GRDC)  Two granted patents on promoters and gene signals for plant biotechnology (CSIRO/ANU and RhoBio Ltd) Publications and Presentations Prof. Waterhouse has published one book (currently editing a second for Wiley-Blackwell), more than 30 book chapters or invited reviews and 101 papers in refereed international journals. Many of these papers and reviews have been in top echelon journals including: Nature, Science, Nature Genetics, Nature Biotechnology, Nature Reviews: Genetics, EMBO, EMBO Reports, Current Biology, PNAS, Trends in Plant Science, Blood and RNA. The Web of Science identifies 82 of these from the last 20 years and records 4626 citations, giving an average ~56 citations/publication and an h-index of 35. In 2003, he was presented with the IMTC- ISI/Thomson award for being the most highly cited CSIRO scientist for the five year period from 1998 to 2003. For each of the last five years, his papers have received between 300 and 400 citations per annum. Prof. Waterhouse has been regularly invited to give, mainly keynote and plenary talks at national and international conferences (>40 since 2000) and to organise and/or chair Symposia and International Conferences. A selection of his publications and talks are given below.

Top ten career-best publications 1. Fusaro AF, Matthew L, Smith NA, Curtin SJ, Dedic-Hagan J, Ellacott GA, Watson JM, Wang M-B, Brosnan C, Carroll BJ, and Waterhouse PM. (2006). RNAi-inducing hairpin RNAs in plants act through the viral defence pathway. EMBO Reports 7 1168-1175 Citations: 41 (IF 7.2) This paper was the first to show that RNAi-inducing hpRNA and viral dsRNA are processed in plants by three different Dicer enzymes.

2. Wang M-B, Bian X-Y, Wu L-M, Liu L-X, Smith NA, Isenegger D, Wu RM, Masuta C, Vance VB, Watson JM, Rezaian A, Dennis ES and Waterhouse PM. (2004) On the role of RNA silencing in the pathogenicity and evolution of viroids and viral satellites. Proc Natl Acad Sci USA 101, 3275-3280. Citations: 63 (IF 9.6) This paper was the first to propose and show that pathogens caused symptoms through siRNAs and the RNAi pathway.

3. Waterhouse PM and Helliwell CA. (2003) Exploring plant genomes by RNA-induced gene silencing. Nature Reviews: Genetics 4, 29-38. Citations: 108 (IF 24.1) This invited review described and compared the various ways of delivering RNAi and discussed how they could be used for functional genomics research.

4. Finnegan EJ, Margis R and Waterhouse PM. (2003). Posttranscriptional Gene Silencing Is Not Compromised in the Arabidopsis Carpel Factory (Dicer-like1) Mutant, a Homolog of Dicer-1 from Drosophila. Current Biology.13, 236-40. Citations: 74 (IF 10.8) This paper showed that, unlike humans which posses a single Dicer, plants have multiple Dicers.

5. Waterhouse PM, Wang M-B and Lough T. (2001) Gene silencing as an adaptive defence against viruses. Nature 411, 834-842. Citations: 423 (IF 31.4) This invited review brought together many previously confusing elements to give a largely cohesive picture of the nature and function of gene silencing (now termed RNAi) in plants, and was the first to draw the parallel with the mammalian immune system.

6. Wesley SV, Helliwell, C, Smith NA, Wang M-B, Rouse D, Liu Q, Gooding P, Singh S, Abbott D, Stoutjesdijk P, Robinson S, Gleave A, Green A and Waterhouse PM. (2001) Constructs for Efficient, Effective and High Throughput Gene Silencing in Plants. The Plant Journal 27, 581-590. Citations: 438 (IF 6.4) Describes the application of intron-spliced hairpin RNA constructs to silence a wide range of genes in a wide range of species, reducing the theory to practice. It also describes the production of a recombinase vector for high throughput silencing such as needed for large scale genomic projects. Doubly cited in Faculty of 1000.

7. Smith NA, Singh SP,Wang M-B, Stoutjesdijk P, Green A and Waterhouse PM. (2000) Total silencing by intron-spliced hairpin RNAs. Nature 407, 319-320. Citations: 385 (IF 31.4) This was the first demonstration that intron-spliced hairpin RNAs direct very efficient gene silencing.

8. Waterhouse PM, Graham MW and Wang M-B. (1998) Virus resistance and gene silencing in plants can be induced by simultaneous expression of sense and antisense RNA. Proc Natl Acad Sci USA 95, 13959-13964. Citations: 486 (IF 9.6) This was the first demonstration that double stranded RNA and hairpin RNA caused gene silencing in plants. This independent study was published only months after the paper by Fire and Mello that showed that double stranded RNA causes gene silencing (RNA interference; RNAi) in nematodes and for which they were awarded the Nobel Prize in 2006.

9. Waterhouse P, Griffiths AD, Johnstone K & Winter G. (1993) Combinatorial infection and in vivo recombination: a strategy for making large phage antibody repertoires. Nucleic Acids Research 21, 2265 – 2266 Citations: 89 (IF 6.8) Describes the invention of an in vivo recombination system which generates combinatorial heavy and light chain antibody libraries. It is key prior art in GatewayTM patents and facilitated the work described in the paper below (10).

10. Griffiths AD, Williams SC, Hartley O, Tomlinson IM, Waterhouse P, Crosby WL, Kontermann RE, Jones PT, Low NM, Allison TJ, Prospero TD, Hoogenboom, HR, Nissim A, Cox JPL, Harrison, JL, Zaccolo M, Gherardi E and Winter, G. (1994) Isolation of high affinity human antibodies directly from large synthetic repertoires. The EMBO Journal 13, 3245 – 3260. Citations: 624 (IF 8.9) Describes the production of a very large library of synthetic antibodies, using the strategy and vectors from (9), and the isolation of high affinity antibodies from it to a number of different antigens.

Five invited opinion pieces 1. Gordon KHJ and Waterhouse PM (2007). RNAi for insect-proof plants. Nature Biotechnology 25, 1233-1234. (IF 22.2) 2. Waterhouse PM and Fusaro AF (2006). Viruses face a double defence by plant small RNAs. Science 313 :54-5. (IF 28.1) 3. Waterhouse PM (2006) Defense and counterdefense in the plant world. Nature Genetics. 38:138-9 (IF 30.2) 4. Hetherington, A and Waterhouse PM (2002). The complexity of signals and levels of gene regulation in plants. Current Opinion in Plant Biology 5, 373-375 (IF 8.7) 5. Finnegan, E.J., Wang, M-B. and Waterhouse PM (2001) Gene Silencing: Fleshing out the bones. Current Biology 11, 99-102. (IF 10.8)

Five recent significant publications 1. Eamens AL, Smith NA, Curtin SJ, Wang M-B, and Waterhouse PM (2009) The Arabidopsis thaliana double-stranded RNA binding protein DRB1 directs guide strand selection from microRNA duplexes. RNA epub doi:10.1261/rna.1646909 (IF 5.0) 2. Pase L, Layton JE, Kloosterman WP, Carradice D, Waterhouse PM, Lieschke GJ. (2009) miR-451 regulates zebrafish erythroid maturation in vivo via its target gata2. Blood. 113 :1794-804. (Cit 4, IF 10.4) 3. Curtin SJ, Watson JM, Smith NA, Eamens AL, Blanchard CL, Waterhouse PM. (2008) The roles of plant dsRNA-binding proteins in RNAi-like pathways. FEBS Letters. 582 2753-60. (Cit 2, IF 3.3) 4. Eamens A, Wang MB, Smith NA, Waterhouse PM. . (2008) RNA silencing in plants: yesterday, today, and tomorrow Plant Physiology 147, 456-68 (Cit 10, IF 6.7) 5. Brosnan CA, Mitter N, Christie M, Smith NA, Waterhouse PM and Carroll BJ. (2007) Nuclear gene silencing directs reception of long-distance mRNA silencing in Arabidopsis. Proc Natl Acad Sci USA 104, 14741-14746 (Cit 32, IF 9.6)

Invited Talks  Five recent plenary talks: Epigenetics-2007, Perth, Australia 2007 International Plant Physiology Meeting, Rio de Janeiro, Brazil, 2007 4th Int. Rice Functional Genomics Meeting, Montpellier, France, 2006 Regulatory RNA Symposium, Taipei, Taiwan, 2006 Functional Genomics of Maize Symposium, Irapuato, Mexico, 2005

 Five recent keynote talks: 56th Annual conference: Genetics Society of Australasia, Brisbane, 2009 Plant and Animal Genome Conference, San Diego, USA, 2008, Invitrogen : Current Topics Symposium 2008, San Diego, USA, 2008 BioAsia 2007, Bangkok, Thailand 2007 COMBIO 2007, Sydney, 2007

 Five talks at “by-invitation-only” conferences US, UK & Aust. Epigenome Conference, Blue Mountains, Australia, 2008 Pattern Formation and Functional Morphology, Linz, Austria, 2008 Banbury Center :RNAi-Related Processes in Plants: Chromatin, Development and Defense, Cold Spring Harbor, USA, 2004. Banbury Center: RNA mediated Silencing, CSH, USA, 2000 FMI & Novartis: Epigenetic Gene Silencing, Brunnen, Switzerland, 2000 Research Achievement In his early work, Waterhouse pioneered an understanding of the genome structure, function and evolution of luteoviruses, oryzaviruses and umbraviruses. He became a world expert for each group, writing their descriptions for AAB/CABI and for the International Committee on Virus Taxonomy (ICTV). He was the first to determine the genomic sequence of the type member of each of the virus groups, identify the functions of most of their genes, and identify novel features like luteoviral coat-protein readthrough and polymerase frame-shifting gene regulation. With this molecular understanding of viruses, he started work on protecting plants against viral infection. He interrupted this to take a sabbatical year with Greg Winter at Cambridge University/Medical Research Centre, where he invented an in vivo and in vitro recombination system that made DNA fragments move from one DNA molecule to another in a totally directed and predictable way. The system created combinatorial libraries of heavy and light chain antibody fragments, expressed on the surface of bacteriophage particles, and yielded high affinity antibodies for medical diagnostic and therapy applications. Two patents have been granted on this work and one of them is key prior art to Invitrogen’s GatewayTM system that is now used for cloning world-wide. After returning to Australia and resuming his virus protection work, Waterhouse and his small research group discovered that, in plants, both transgene-mediated virus resistance and gene silencing was induced and targeted by double-stranded RNA (dsRNA). This result was reported in a landmark paper in the prestigious general journal Proc. Natl Acad. Sci. USA in 1998, and described by Nobel Laureate Phillip Sharp as “The purest demonstration that dsRNA mediates gene silencing in plants”. In this paper, they not only demonstrated that dsRNA induced gene silencing, but also showed that this could be triggered by single stranded RNA designed to form a self-complementary hairpin (hp)RNA expressed from transgenes, and provided the first model for a targeted RNA cleavage by an RNA-bearing endonuclease. In the same year, but published a few months earlier, Andy Fire and Craig Mello, in the USA, showed that injection of dsRNA induced the silencing of genes in nematodes, a phenomenon they called RNA interference (RNAi). This finding in animals earned Fire and Mello the Nobel Prize for Medicine (2006). Recognizing the power of efficient directed gene silencing, Waterhouse pioneered the use of hpRNA constructs for gene silencing and his construct design and/or vectors have been adopted worldwide for gene silencing in plants, and in animals such as Drosophila. His group has used hpRNA constructs to make plants that are virus-immune or altered in their metabolic or signal transduction pathways. The vectors have also been used by academic and industry researchers, often in collaboration with the Waterhouse group, for a wide spectrum of applications ranging from functional genomics to the creation of blue roses. Eleven families of patents arising from this work, with Waterhouse as a named inventor, are currently granted or being processed, although the predominant patent for RNAi is still being contested with Fire and Mello in the USA. More recently, Prof. Waterhouse has been investigating the roles of the different small RNAs and genes involved in RNAi and epigenetic regulation pathways. With his colleagues, he has shown that viroids cause symptoms in plants by inducing RNAi against the plant host's endogenous genes, solving the long-standing mystery of how a viroid pathogen, which encodes no protein, can cause symptoms; this heralded the way for researchers to find that animal viruses also affect their hosts through the RNAi and microRNA pathways. He has also identified that plants contain a set of four major types of Dicer enzymes that generate differently sized small RNAs to guide viral defence, RNAi and chromatin modification, that a family of dsRNA binding proteins play important roles in regulating these processes, and that there is a mobile signal that can induce RNA silencing in distal tissues using enzymes normally associated with epigenetic DNA silencing.

Ability to build world class research teams Prof Waterhouse has been building and leading world-class research teams for over 15 years. Some teams, such as his own research units, have been small groups of researchers working together on fundamental science projects that have had a substantial impact on the international stage. This impact is measured in his publication record and the frequency with which he is invited to present his work at international meetings. Other teams have required his leadership and governance of larger groups (of around 40 people) from different laboratories who were united under a common theme (e.g. as Leader of the Defence Program of the CRC for Plant Science, Canberra, and as Leader of the Plant Defence Program, CSIRO).

Supervision and mentoring. Prof. Waterhouse has a strong record in research training and mentorship and a passion for inspiring and developing young minds. He has supervised 6 PhD students and more than 20 post doctoral fellows during his time at CSIRO. Many have gone on to establish their own labs and others are young researchers in different public or private research organisations around the world. Since moving to Sydney last year, he has taken two honours students to First Class honours, hosted an Endeavour Fellow from Canada, taken on the supervision of three PhD students, and played an interactive and lecturing role with the international summer school students in the Harry Messel “Genes to Galaxies” project.

Community Engagement and Outreach Prof. Waterhouse has a history of excellent communication with students, industry groups, government, media and the public. Among the many invitations to talk at international and national conferences, a number have been by student request such as the 16th Penn State Symposium RNA Biology: Novel Insights from Plant Systems, USA, 2006, others have been in response to requests by industry groups such as the National Farmers Federation, and by public groups like the Canberra Organic Growers Society. As a result of his science, awards and profile, Prof. Waterhouse has also had discussions with and/or given presentations or reports to Prime Ministers, Federal Ministers for Science, and Government agencies like FSANZ and OGTR, and given many interviews to or featured in national and international electronic and print media.