Achievements of Recent Alumni on the Rotation PhD Programme

 

Frank Sainsbury

frank-sainsburyFrank joined the Rotation Student Programme in October 2004, having completed his first degree at the University of Sydney, Australia. The impact of Frank’s thesis research has been dramatic. In particular, it has led to the development of a non-replicating virus-derived vector that provides extremely high-level protein production in plants. The new CPMV-HT expression system has been adopted worldwide for the rapid expression of high value protein components. Examples of important applications include the safe development of animal vaccines and the production of antibodies for therapeutic purposes.

Frank Sainsbury was awarded the 2009 student prize for Excellence in Scientific Research in recognition of outstanding innovations on plant-based expression systems in the laboratory of his PhD supervisor, Professor George Lomonossoff. His next career move was to a post-doctoral position at the University of Laval, Canada, where he continued his exciting studies on the production of high-value proteins in plants. He then returned to Australia as a UQ Postdoctoral Fellow, developing virus-like particles (VLPs) into more efficacious vaccines and novel therapeutics.

Frank commented: “I really enjoyed my PhD studentship at the John Innes Centre because I was given the opportunity to chose the direction of my studies through the rotation student programme and was provided with the most fantastic research support and facilities.”

 

Major Publications from PhD Research

The research that Frank undertook during his PhD resulted in four first-author publications in refereed journals and three oral presentations at international meetings. There have also been two review articles on which he is first-author and a patent application on which he is a named inventor. The technology has been licensed through Plant Bioscience Ltd to the Canadian Biotechnology Company, Medicago Inc.

 

Aljabali A. A. A., Sainsbury F., Lomonossoff G., Evans D. J.(2010) Cowpea mosaic virus unmodified empty viruslike particles can be loaded with metal and metal oxide. Small 6 818-821.

Saunders K., Sainsbury F., Lomonossoff G. P.(2009) Efficient generation of cowpea mosaic virus empty virus-like particles by the proteolytic processing of precursors in insect cells and plants. Virology 393 329-37.

Sainsbury F., Liu L., Lomonossoff G. P.(2009) Cowpea mosaic virus-based systems for the expression of antigens and antibodies in plants Methods in Molecular Biology (Editors: Faye L.) Humana Press Inc. 483 25-39.

Sainsbury F., Thuenemann E. C., Lomonossoff G. P. (2009) pEAQ: versatile expression vectors for easy and quick transient expression of heterologous proteins in plants Plant Biotechnology Journal 7 682-693.

Mugford S. T., Qi X., Bakht S., Hill L., Wegel E., Hughes R. K., Papadopoulou K., Melton R., Philo M., Sainsbury F., Lomonossoff G. P., Roy A. D., Goss R. J., Osbourn A.(2009) A serine carboxypeptidase-like acyltransferase is required for synthesis of antimicrobial compounds and disease resistance in oats. Plant Cell 21 2473-2484.

Mugford S. T., Qi X., Bakht S., Hill L., Wegel E., Hughes R. K., Papadopoulou K., Melton R., Philo M., Sainsbury F., Lomonossoff G. P., Roy A. D., Goss R. J., Osbourn A.(2009) A serine carboxypeptidase-like acyltransferase is required for synthesis of antimicrobial compounds and disease resistance in oats. Plant Cell 21 2473-84.

Sainsbury F., Lavoie P-O., D’Aoust M-A., Vezina L-P., Lomonossoff G. P.(2008) Expression of multiple proteins using full-length and deleted versions of cowpea mosaic virus RNA-2 Plant Biotechnology Journal 6 82-92.

Sainsbury F., Lomonossoff G. P.(2008) Extremely high-level and rapid transient protein production in plants without the use of viral replication Plant Physiology 148 1212-1218.

Sainsbury F., Canizares M. C., Lomonossoff G. P.(2007) Cowpea mosaic virus-based expression vectors Virus Expression Vectors (Editors: Hefferon, Kathleen L.) Research Signpost, India 339-355.

Sainsbury F., Tattersall A. D., Ambrose M. J., Turner L., Ellis T. H. N., Hofer J. M. I.(2006) A crispa null mutant facilitates identification of a crispa-like pseudogene in pea Functional Plant Biology 33 757-763.

 

Alex Graf

alex-grafAlex joined the rotation student PhD programme at JIC in October 2005, having completed his first degree at the Martin Luther University, Germany. Working in the laboratory of Professor Alison Smith, Alex used simple yet powerful experimental approaches to link several aspects of plant biology that had previously been studied separately – carbohydrate metabolism, the circadian clock and the control of plant growth and development. The result is a new perspective on the relationship between plant productivity and the diurnal cycle of photosynthesis and nocturnal starch breakdown. Alex’s results, which were published in PNAS, have opened up entirely new avenues of research which are currently being explored through new research funding. In 2010, he was awarded the John Innes Student Prize for Excellence in Research. Following a post-doctoral position at the ETH laboratory in Zurich he became a Research Group Leader at the Max Planck Institute of Molecular Plant Physiology in Potsdam.

Alex commented: “I enjoyed my time as a rotation student at JIC because it was the perfect environment for a successful PhD where cutting edge technology meets experience and creative thinking.”

 

Major Publications from PhD Research

Comparot-Moss S., Kötting O., Stettler M., Edner C., Graf A., Weise S. E., Streb S., Lue W. L., MacLean D., Mahlow S., Ritte G., Steup M., Chen J., Zeeman S. C., Smith A. M.(2010) A putative phosphatase, LSF1, is required for normal starch turnover in Arabidopsis leaves. Plant Physiology 152 685-97.

Graf A., Schlereth A., Stitt M., Smith A. M.(2010) Circadian control of carbohydrate availability for growth in Arabidopsis plants at night. Proceedings of the National Academy of Sciences USA 107 9458-63.

Jaeger K. E., Graf A., Wigge P. A.(2006) The control of flowering in time and space Journal of Experimental Botany 57 3415-3418

 

 

Sebastian Marquardt

Sebastian_sepSebastian joined the rotation student PhD programme at JIC in October 2005. Working with his supervisor, Professor Caroline Dean, he used a forward genetic approach to dissect an RNA-mediated chromatin silencing pathway involved in the control of flowering time. Sebastian was able to identify several new genetic components that link a histone demethylase activity with the co-transcriptional processing of nascent noncoding transcripts. The results, which have been published in the high-impact journals PNAS and Science, have broad relevance for understanding the control of gene expression by noncoding RNA and chromatin modification in animals, fungi and plants. Sebastian joined JIC from the Max Planck Institute, Cologne. In 2010, Sebastian was awarded the John Innes Student Prize for Excellence in Research. He continued his research career at Harvard Medical School, where he is currently studying the expression of cryptic non-coding RNAs in the Buratowski lab.  He then started his own group at the University of Copenhagen Plant Science Centre.

He commented: “My time as a research student at the JIC was fantastic. Doors were always open and I could receive a lot of support in pursuit of my developing interests”.

 

Major Publications from PhD Research

Liu F., Marquardt S., Lister C., Swiezewski S., Dean C.(2010) Targeted 3′ processing of antisense transcripts triggers Arabidopsis FLC chromatin silencing Science 327 94-97

Manzano D., Marquardt S., Jones A. M., Baurle I., Liu F., Dean C.(2009) Altered interactions within FY/AtCPSF complexes required for Arabidopsis FCA-mediated chromatin silencing Proceedings of the National Academy of Sciences USA 106 8772-7

Marquardt S., Boss P. K., Hadfield J., Dean C.(2006) Additional targets of the Arabidopsis autonomous pathway members FCA and FY Journal of Experimental Botany 57 3379-3386

 

 

Lucy Foulston

lucy-foulstonLucy came to JIC with a 1st Class Honours Degree from the University of Oxford. Through the rotation student PhD programme she elected to work with Professor Mervyn Bibb  characterising the gene cluster for biosynthesis of microbisporicin, an unusual peptide lantibiotic made by the rare actinomycete Microbispora corallina. Lucy identified the gene cluster by genome scanning and subsequently achieved heterologous expression in a strain of Nonomuraea (a related actinomycete), thereby defining the minimal set of genes required for microbisporicin biosynthesis. She then established, de novo, a framework for the genetic analysis of M. corallina, and isolated a number of mutants that revealed interesting aspects of regulation and self-resistance (immunity) for the antibiotic pathway. Because of Lucy’s efforts, we now have a very good idea of how microbisporicin is made, and how that process is regulated. Lucy’s work will undoubtedly lead to knowledge‐based approaches to improve antibiotic yield, which will be crucial as the compound moves into clinical trials. Further genetic manipulation of the biosynthetic pathway in M. coralline will also allow the generation of microbisporicin derivatives with potentially improved clinical properties. Lucy’s thesis exemplifies how it is possible for a graduate student to carry out excellent fundamental science that has clear strategic impact.

Lucy was awarded the John Innes Foundation student prize for Excellence in Scientific Research (2011).

She commented: “It is such an honour to be given this award. My time at JIC was extremely rewarding both scientifically and personally.” Lucy went on to undertake postdoctoral research at Harvard Medical School with Richard Losick, studying biofilm formation by a pathogen, Staphylococcus aureus.  She then went on to work with WarpDrive Bio in the US.

 

Major Publications from PhD Research

Her PhD research has resulted in first-author publications in PNAS and Journal of Bacteriology (with accompanying front cover).

 

 

Benjamin Schwessinger

Ben-SchwessingerBen joined the John Innes Centre/ Sainsbury Laboratory as a rotation student from Glasgow University in 2006, undertaking short placements during his first year with Professors Jones, Oldroyd and Kamoun. He then joined the research group of Cyril Zipfel in the Sainsbury Laboratory in order to work on the molecular genetics of pathogen-associated molecular pattern (PAMP)-triggered immunity. His work focussed on a particularly interesting mutant of Arabidopsis that was impaired in both flg22- and elf18-derived PAMP responses. It soon became apparent from map-based cloning that the mutation corresponded to a new allele of BAK1 (a previously known regulator of PAMP-triggered immunity). Phenotypic characterisation of this novel allele, bak1-5, revealed new and important insights into the role of BAK1 in different signalling pathways. Bak1-5 is strongly impaired in PAMP-triggered immunity pathways (dependent on either FLS2- or EFR) but apparently displays wild-type signalling capacity in two other BAK1-dependent pathways, namely brassinosteroid (BR) signalling and BAK1-dependent cell death control. Further studies indicated that protein phosphorylation associated with the regulatory receptor-linked kinase BAK1 is probably the basis for differential signalling in BR, innate immunity and cell death control. Further work at the Sainsbury Laboratory will exploit the unique properties of BAK1-5 to investigate the role of phosphorylation in early immune signalling.

Ben was awarded the John Innes Foundation student prize for Excellence in Scientific Research (2011) and became an HSFP Postdoctoral Fellow in the Pam Ronald lab at the University of California, Davis, before moving on to the Australian National University.

 

Major Publications from PhD Research

This work has led to first-authored publications in PLoS Genetics and Plant Cell.

 

 

Tung Le

Tung-LeTung Le joined the JIC/TSL Rotation PhD programme in October 2007 having gained a first class degree from the University of Birmingham. Following his rotation year, he joined Mark Buttner’s lab in 2008 to work on the molecular basis of resistance to the antibiotic simocyclinone in the producing organism Streptomyces antibioticus.

To execute the work covered in his thesis, Tung had to master molecular genetics, biochemistry, and a great deal of structural biology. In order to address one of the key questions in his research, namely the role of the N-terminal region of the regulatory protein SimR, Tung wrote and won both an EMBO Short-Term Travel Fellowship and a Korner Travel Fellowship to fund a 10-week trip to the lab’s of Prof. Dick Brennan and Prof. Maria Schumacher (Houston, USA), who are internationally acknowledged experts in the crystallography of DNA-protein complexes. Through this trip, Tung crystallised and solved the structure of the SimR-DNA complex, and discovered that the N-terminal extension of SimR binds in the minor groove adjacent to the major groove occupied by the classical HTH motif.

In 2011, Tung was awarded the John Innes Foundation Prize for Excellence in Scientific Research. Tung’s external examiner described his work as “a technical tour de force” showing “outstanding levels of achievement throughout the thesis”. This was echoed by the internal examiner who concluded that “Tung has a great future ahead of him”.

Tung became a post-doc in Prof. Mike Laub’s lab at MIT and joins the John Innes Centre as a Project Leader in 2016. He therefore follows in the footsteps of Yiliang Ding, who was the first former rotation student to return as a Project Leader.

 

Major Publications from PhD Research

On the basis of his thesis work, Tung published four excellent 1st-author papers (in Molecular Microbiology, Journal of Molecular Biology, Nucleic Acids Research and Acta Crystallographica) and he was also a minor author on a fifth paper (in Science). His supervisor stressed that “Tung was almost entirely responsible, both intellectually and technically, for the direction of his work, and that his four first-author papers should be seen as the product of his own vision and efforts.”

 

 

Yang Zhang

Yang joined the Rotation PhD programme in October 2009, having previously studied at Sichuan University, China. Yang has been an exceptional student at JIC, with a strong desire to undertake fundamental research with end-use applications. During his rotation year, he undertook excellent research projects on wheat flowering time (with David Laurie) and on Arabidopsis heat-stress genes (with Isabel Baurle). For his major research project, he then joined Cathie Martin’s lab in order to study the roles of flavonoids in determining the shelf life of tomato fruit.

Through his insight and diligence, Yang discovered an amazing amount about the mechanisms governing over-ripening and resistance to soft-rot in tomatoes. This in turn has provided new strategies for improving the shelf life of soft fruit, which could have a major impact on breeding programmes and hopefully lead to varieties that can be kept for longer, so reducing food waste. By the introduction of genes encoding Delila and Rosea 1, two transcription factors from Antirrhinum, Yang showed that accumulation of anthocyanins in tomato fruit doubled the shelf-life, delayed over-ripening and reduced susceptibility to the fungal pathogen, Botrytis cinerea. Furthermore, he showed that delayed over-ripening was associated with high anti-oxidant capacity, whereas reduced susceptibility to fungal attack was due to the high scavenging ability of particular anthocyanins. As a side-project to his PhD research, Yang also investigated the origin of anthocyanin-rich blood oranges, demonstrating that the Chinese varieties arose independently from Mediterranean blood oranges. Yang presented his work at the International Congress on Plant Metabolism in Qingdao (2012), China and at the Gordon Conference on Plant Metabolic Engineering, New Hampshire (2013).

In 2014, Yang was awarded the John Innes Prize for Excellence in Research. His PhD examiner described his work as “providing some very exciting and novel results which are of great interest from the point of view of post-harvest food quality and human nutrition”. He continued his research as a postdoctoral scientist in the laboratory of Cathie Martin.

Yang Commented: The 4-year Rotation PhD Programme totally changed my scientific view. When I first arrived at JIC, I was only aware of the field of crop science, from my previous experience. But with the work in three different labs during my rotation year, I entered the world of plant metabolism. During my PhD, I combined techniques of plant metabolism and crop science to establish my own inter-disciplinary research project. I was very interested in how plant secondary metabolites can contribute to enhance the agronomic traits of crops. Thanks to this Rotation PhD programme, I managed to link my old research experience to new fields. This unique experience is a precious treasure in my research career.

 

Major Publications from PhD Research

Yang’s data has been published in Current Biology and New Phytologist with further publications in the pipeline.  On the basis of his PhD work, Yang has contributed to four refereed publications and several reviews, including a major review on “Plants diet and health” for the Annual Review of Plant Biology.

Zhang,Y., Butelli, E and Martin, C. (2014). Engineering anthocyanin biosynthesis in plants. Current Opinion in Plant Biology 19, 81-90

 Zhang, Y., Butelli, E., De Stefano, R., Schoonbeek, H.-j., Magusin, A., Pagliarani, C., Wellner, N., Hill, L., Orzaez, D., and Granell, A. (2013). Anthocyanins Double the Shelf Life of Tomatoes by Delaying Overripening and Reducing Susceptibility to Gray Mold. Current Biology 23, 1094-1100.

Bassolino, L*., Zhang, Y*., Schoonbeek, H.j., Kiferle, C., Perata, P., and Martin, C. (2013). Accumulation of anthocyanins in tomato skin extends shelf life. New Phytologist 200, 650-655. (*co-first author)

Martin, C., Zhang, Y., Tonelli, C., and Petroni, K. (2013). Plants, Diet, and Health. Annual review of plant biology 64, 19-46.

Turner, A.S., Faure, S., Zhang, Y., and Laurie, D.A. (2013). The effect of day-neutral mutations in barley and wheat on the interaction between photoperiod and vernalization. Theoretical and Applied Genetics 126, 2267-2277.

Butelli, E., Licciardello, C., Zhang, Y., Liu, J., Mackay, S., Bailey, P., Reforgiato-Recupero, G., and Martin, C. (2012). Retrotransposons control fruit-specific, cold-dependent accumulation of anthocyanins in blood oranges. The Plant Cell 24, 1242-1255.

 Martin, C., Zhang, Y., Tomlinson, L., Kallam, K., Luo, J., Jones, J.D., Granell, A., Orzaez, D., and Butelli, E. (2012). Colouring up Plant Biotechnology. Recent Advances in Polyphenol Research 3, 131.

 

Conferences attended during PhD:

2nd International Conference on Plant Metabolism (2011.07), Qingdao, China.
1st ATHENA Project Annual Meeting (2011.10), Sicily, Italy
National Agri-Science Chemical Biology Postgraduate Symposium (2012.11),  London, UK
Gordon Research Conference on Plant Metabolic Engineering (2013.07), NH, United States
1st Norwich & Cambridge Student Symposium on Plant & Microbial Biology (2013.07), Norwich UK.