|2008 - present||Director||CNAP, Department of Biology, University of York|
|2003 - 2008||Deputy director||CNAP, Department of Biology, University of York|
|1999 - present||Chair of Biochemical Genetics||CNAP, Department of Biology, University of York|
|1998 - 1999||Senior Lecturer||Division of Biochemistry and Molecular Biology, University of Glasgow|
|1994||SERC/NATO funded research scientist||Department of Plant Biology, Carnegie Institute, Stanford|
|1993 - 1998||Lecturer||Division of Biochemistry and Molecular Biology, University of Glasgow|
|1990 - 1993||Post-doctoral research fellow||Department of Plant Science, University of Oxford|
|1986 - 1989||PhD||PhD Department of Botany, University of Edinburgh|
|1982 - 1986||BSc First Class Honours in Botany and Genetics||The Queens University Belfast|
Plants make an amazing array of chemical structures, and we are interested in working out how they do this, plus how we can develop them to make useful molecules. I have two main areas of interest, one focused on understanding the regulation of processes associated with seed germination and the other focused on discovering and improving the production of high value chemicals in plants. Current projects range from lipid signals that control seed germination to the development of novel oilcrops such as Jatropha curcas and medicinal crops such as Artemisia annua and Papaver somniferum (opium poppy).
We have recently discovered that an oxylipin signaling molecule, OPDA, plays an important role in regulating seed dormancy and germination by modulating the levels of the ABI5 transcription factor in Arabidopsis seeds (Dave et al., 2011). BBSRC funded research is now focused on establishing the role of OPDA in the control of seed germination by environmental signals.
With funding from the Bill and Melinda Gates Foundation, we have developed improved varieties of the Artemisia annua plant, which is the source of artemisinin, the World Health Organisation recommended drug that kills the malaria parasite. Our studies have resulted in the first genetic map for the plant, published in the leading journal Science in 2010, and a partnership with industry that is delivering improved hybrid seed into the developing world supply chain (see project website for further details: http://www.york.ac.uk/org/cnap/artemisiaproject/index.htm).
In partnership with GlaxoSmithKline Australia, we have recently discovered the genetic basis for production of the antitussive and anticancer compound noscapine in opium poppy. A ten gene cluster encoding five different enzyme classes has evolved to produce noscapine, which is currently in early stage clinical trials in the USA. This breakthrough, published in the journal Science in 2012, will lead to the improved production of noscapine and related bioactive molecules.
A sustainable supply of artemisinin from high-yield Artemisia annua for treatment of malaria
Funding body: Bill & Melinda Gates Foundation
Jatropha curcas Applied and Technological Research on Plant Traits (JATROPT)
Funding body: EU
Molecular breeding of a commercial pharmaceutical crop
Funding body: GlaxoSmithKline
The role of the oxylipin OPDA in the seasonal sensitivity of seed dormancy
Funding body: BBSRC
Multipurpose crops for industrial bioproducts and biomass (MultiHemp)
Funding body: EU
Using wild ancestor plants to make rice more resilient to increasingly unpredicable water availability
Funding body: BBSRC, DFID and (through a grant to the BBSRC) the Bill & Melinda Gates Foundation, under the Sustainable Crop Production Research for International Development (SCPRID) programme, a joint initiative with the Department of Biotechnology of the Government of India's Ministry of Science and Development
|Senior Research Administrator||Judith Mitchell (full time)|
|Post doctoral fellow||Dr Anuja Dave (full time)||The role of the oxylipin OPDA in the seasonal sensitivity of seed dormancy|
|Post doctoral fellow||Dr Fabian Vaistij (full time)|
|Post doctoral fellow||Dr Zhesi He (full time)||Molecular breeding of a commercial pharmaceutical crop|
|Post doctoral fellow||Dr Andrew King (full time)||Jatropha curcas Applied and Technological Research on Plant Traits (JATROPT)|
|Post doctoral fellow||Dr Tony Larson (full time)||Head of CNAP Metabolite Profiling Unit|
|Post doctoral fellow||Dr Roxana Teodor (full time)||Molecular breeding of a commercial pharmaceutical crop|
|Post doctoral fellow||Dr Thilo Winzer (full time)||Head of CNAP Molecular Breeding Unit|
|Student||Jasper Clarke||QTL mapping in Jatropha curcas|
|Student||Vicki Springthorpe||Arabidopsis molecular phenology|
Biosynthetic regulation in a commercial pharmaceutical crop
Regulation of seed dormancy and germination
|Technician||Alison Gilday (full time)||The role of the oxylipin OPDA in the seasonal sensitivity of seed dormancy|
|Technician||Valeria Gazda (full time)||Molecular breeding of a commercial pharmaceutical crop|
|Technician||Molecular breeding of a commercial pharmaceutical crop|
|Technician||Filip Kaminski (full time)||Multipurpose crops for industrial bioproducts and biomass (MultiHemp)|
Seed Germination and Oil Mobilisation (for 2012 - 13)
Supervisor: Professor Ian Graham
Plants have evolved to alter how they grow and develop in response to signals from the environment. A good example of this is the process of seed germination, which marks the start of growth following a period of quiescence or dormancy. Seed dormancy controls the timing of germination and provides an important adaptive strategy for survival during periods of unfavourable environmental conditions. Seed dormancy is also an extremely important trait for crop improvement since it controls pre-harvest sprouting and the uniformity of seed germination and seedling growth.
In the model plant Arabidopsis thaliana dormancy is induced during the seed maturation phase and is highest in freshly harvested seeds. The dormancy block on germination is removed by imbibing seeds at low temperatures (stratification). In nature this ensures that seeds only germinate in spring when conditions are good for growth. Dormancy is also removed following prolonged periods of dry storage referred to as after-ripening. Two plant hormones play a crucial, antagonistic role in regulating dormancy/germination: abscisic acid (ABA) promotes dormancy and inhibits germination, whereas gibberellin (GA) promotes germination. We have made a number of important discoveries about the underlying molecular mechanisms associated with the control of seed dormancy and germination including identifying specific roles for transcription factors such as SPATULA, DELLAS and ABA-INSENSITIVE-4 (Penfield et al., 2005, 2006a, 2006b). We have also recently discovered that a lipid based signalling molecule, OPDA, interacts with ABA to regulate dormancy status (Dave et al., 2011).
A much better known role for lipids in oilseed plants such as A. thaliana and the close relative oilseed rape is as a storage reserve. Lipids, in the form of triacylglycerol (TAG), accumulate during seed development and are mobilised to sucrose upon seed germination. Mobilisation of TAG to sugar involves the coordinated induction of a number of biochemical pathways in different subcellular locations (Graham, 2008). Fatty acids are released from TAG by lipolysis, enter the peroxisome through the ABC transporter protein PXA1, and are converted to acetyl-CoA in a process involving fatty acid ß-oxidation. pxa1 mutant seeds are defective in seedling establishment because they are unable to convert TAG to sugar, which is needed to support growth. This phenotype is rescued by exogenously applied sugar.
Our investigations are now focussed on how different regulatory components interact to control seed germination and oil mobilisation. This PhD studentship will further our knowledge of seed germination in Arabidopsis and should also lead to the identification of key genes that can be targeted for crop improvement. Techniques such as chromatin-immuno precipitation (ChIP) will be used to identify the targets of transcription factors that we know play a key role in the control of germination based on mutant phenotype. Resulting data will be compared with transcriptomic datasets from mutant and wild type plants to identify common gene targets. The student will receive a comprehensive training in seed biology, molecular and biochemical genetics and bioinformatic analysis of large datasets.
Dave, A., Hernandez, L., He, Z., Andriotis, V.M., Vaistij, F.E., Larson, T.R., Graham, I.A. (2011). 12-oxo-phytodienoic acid (OPDA) accumulation during seed development represses seed germination in Arabidopsis. Plant Cell, 23: 583-599.
Graham, IA (2008). Seed storage oil mobilization. Annual Review of Plant Biology 59: 115-42.
Penfield. S., Josse, E.M., Kannangara, R., Gilday, A., D., Halliday, K.J., Graham, I.A. (2005). Cold and light control seed germination through the bHLH transcription factor SPATULA. Current Biology 15: 1998-2006.
Penfield, S., Gilday, A., Halliday, K., Graham, I.A. (2006). DELLA mediated cotyledon expansion breaks coat-imposed seed dormancy. Current Biology, 16: 2366-70.
Penfield, S., Li, Y., Gilday, A.D., Graham, S. and Graham, I. A. (2006). Arabidopsis ABA INSENSITIVE 4 regulates lipid mobilization in the embryo and reveals repression of seed germination by the endosperm. Plant Cell, 18:1887-99.
For further information please see: http://www.york.ac.uk/biology/centrefornovelagriculturalproducts/training/
Recent articles in refereed journals
Larson, T.R, Branigan, C., Harvey, D., Penfield, T., Bowles, D., Graham, I.A. (2013). A survey of artemisinic and dihydroartemisinic acid contents in glasshouse and global field-grown populations of the artemisinin-producing plant Artemisia annua. Industrial Crops and Products, 45: 1-6.
Brown AP, Kroon JTM, Swarbreck D, Febrer M, Larson TR, Graham IA, Caccamo M, Slabas AR. (2012). Tissue-specific whole transcriptome sequencing in castor, directed at understanding triacylglycerol lipid biosynthetic pathways. PLoS ONE 7 (e30100).
De Rybel, B, Audenaert, D, Xuan, W, Overvoorde, P, Strader, LC, Kepinski, S, Hoye, R, Brisbois, R, Parizot, B, Vanneste, S, Liu, X, Gilday, A, Graham, IA, Nguyen, L, Jansen, L, Njo, MF, Inzé, D, Bartel, ., Beeckman, T. (2012). A role for the root cap in root branching revealed by the non-auxin probe naxillin. Nat Chem Biol. 8: 798-805.
Hernandez ML, Whitehead L, He Z, Gazda V, Gilday A, Kozhevnikova E, Vaistij FE, Larson TR, Graham IA. (2012). A cytosolic acyltransferase contributes to triacylglycerol synthesis in sucrose-rescued Arabidopsis seed oil catabolism mutants. Plant Physiol. 160: 215-25.
Hooks, KB, Turner, JE, Graham, IA, Runions, J, Hooks, MA. (2012). GFP-tagging of Arabidopsis acyl-activating enzymes raises the issue of peroxisome-chloroplast import competition versus dual localization. Plant Physiol. [Epub ahead of print] PubMed PMID: 22920973.
Mai K, Andres J, Bobbert T, Assmann A, Biedasek K, Diederich S, Graham IA, Larson TR, Pfeiffer AF, Spranger J. (2012). Rosiglitazone increases fatty acid Δ9-desaturation and decreases elongase activity index in human skeletal muscle in vivo. Metabolism, 61: 108-16.
Moreno-Pérez AJ, Venegas-Calerón M, Vaistij FE, Salas JJ, Larson TR, Garcés R, Graham IA, Martínez-Force E. (2012). Reduced expression of FatA thioesterases in Arabidopsis affects the oil content and fatty acid composition of the seeds. Planta, 235: 629-39.
Penfield, S, Clements, S, Bailey, K, Gilday, A, Leegood, R, Gray, J, Graham, IA. (2012). Expression and manipulation of PHOSPOENOLPYRUVATE CARBOXYKINASE 1 identifies a role for malate metabolism in stomatal closure. Plant J. 69: 679-88.
Sanchez-Ortiz A, Romero-Segura C, Gazda VE, Graham IA, Sanz C, Perez AG. (2012). Factors limiting the synthesis of virgin olive oil volatile esters. J Agric Food Chem. 60: 1300-07.
Winzer T, Gazda V, He Z, Kaminski F, Kern M, Larson TR, Li Y, Meade F, Teodor R, Vaistij FE, Walker C, Bowser TA, Graham IA. (2012). A Papaver somniferum 10-gene cluster for synthesis of the anticancer alkaloid noscapine. Science 336: 1704-8.
Allen E, Moing A, Wattis JA, Larson T, Maucourt M, Graham IA, Rolin D, Hooks MA. (2011). Evidence that ACETATE NON-UTILIZING 1 prevents carbon leakage from peroxisomes during lipid mobilization in Arabidopsis seedlings. Biochemical J. 437: 505-13.
Araújo WL, Ishizaki K, Nunes-Nesi A, Tohge T, Larson TR, Krahnert I, Balbo I, Witt S., Dörmann P, Graham IA, Leaver CJ, Fernie AR. (2011). Analysis of a range of catabolic mutants provides evidence that phytanoyl-coenzyme A does not act as a substrate of the electron-transfer flavoprotein/electron-transfer flavoprotein:ubiquinone oxidoreductase complex in Arabidopsis during dark-induced senescence. Plant Physiol. 157: 55-69.
Dave A, Hernandez L, He Z, Andriotis VM, Vaistij FE, Larson TR, Graham IA. (2011). 12-oxo-phytodienoic acid (OPDA) accumulation during seed development represses seed germination in Arabidopsis. Plant Cell 23: 583-599.
He W, King AJ, Khan AM, Cuevas JA., Ramiaramanana D, Graham IA. (2011). Analysis of phorbol-ester content, curcin content and genetic diversity, in edible and non-edible accessions of Jatropha curcas (L.) from Madagascar and Mexico. Plant Physiol Biochem 49: 1183-1190.
Josse EM, Gan Y, Bou-Torrent J, Stewart KL, Gilday AD, Jeffree CE, Vaistij FE, Martínez-García JF, Nagy F, Graham IA, Halliday KJ. (2011). A DELLA in Disguise: SPATULA Restrains the Growth of the Developing Arabidopsis Seedling. Plant Cell 23: 1337-51.
Kendall SL, Hellwege A, Marriot P, Whalley C, Graham IA, Penfield SD. (2011). Induction of dormancy in Arabidopsis summer annuals requires parallel regulation of DOG1 and hormone metabolism by low temperature and CBF transcription factors. Plant Cell 23: 2568-80.
King AJ, Li Y, Graham IA. (2011). Profiling the developing Jatropha curcas L. seed transcriptome by pyrosequencing. BioEnergy Research 4: 211-221.
Araújo, WL, Ishizaki, K, Nunes-Nesi, A, Larson, TR, Tohge, T, Krahnert, I, Witt, S, Obata, T, Schauer, N, Graham, IA, Leaver, CJ, Fernie, AR. (2010). Identification of the 2-Hydroxyglutarate and Isovaleryl-CoA Dehydrogenases as Alternative Electron Donors Linking Lysine Catabolism to the Electron Transport Chain of Arabidopsis Mitochondria. Plant Cell 22: 1549-1563.
Gómez, L, Gilday, A, Feil, R, Lunn, J, Graham, IA. (2010). AtTPS1 mediated trehalose-6-phosphate synthesis is essential for embryogenic and vegetative growth and responsiveness to ABA in germinating seeds and stomatal guard cells. Plant J. 64: 1-13.
Graham, IA, Besser, K, Blumer, S, Branigan, CA, Czechowski, T, Elias, L, Guterman, I, Harvey, D, Isaac, PG, Khan, AM, Larson, TR, Li, Y, Owens, S, Pawson, T, Penfield, T, Rae, AM, Rathbone, DA, Ross, J, Smallwood, MF, Segura, V, Townsend, T, Vyas, D, Winzer, T, Bowles, D. (2010). The genetic map of Artemisia annua L. identifies multiple loci affecting yield of the antimalarial drug artemisinin. Science 327: 328-331.
King, AJ, Cragg, SM, Li, Y, Dymond, J, Guille, MJ, Bowles, DJ, Bruce, NC, Graham, IA, McQueen-Mason, SJ. (2010). Molecular insight into lignocellulose digestion by a marine isopod in the absence of gut microbes. PNAS 107: 5345-5350.
Maia, MR, Chaudary, LC, Bestwick, CS, Richardson, AJ, McKain, N, Larson, TR, Graham, IA, Wallace, RJ. (2010), Toxicity of unsaturated fatty acids to the biohydrogenating ruminal bacterium, Butyrivibrio fibrisolvens. BMC Microbiology 10(1): 52.
Scott, IM, Vermeer, CP, Liakata, M, Corol, DI, Ward, JL, Lin, W, Johnson, HE, Whitehead, L, Kular, B, Baker, JM, Walsh, S, Dave, A, Larson, TR, Graham, IA, Wang, TL, King, RD, Draper, J, Beale, MH. (2010). Enhancement of plant metabolite fingerprinting by machine learning. Plant Physiol. 153: 1506-20.
Sidaway-Lee, K, Josse, E-M, Brown, A, Halliday, KJ, Graham, IA, Penfield, S. (2010). SPATULA links daytime temperature and plant growth rate. Current Biology 20: 1493-1497.
Troufflard, S, Mullen, W, Larson, TR, Graham, IA, Crozier, A, Amtmann, A, Armengaud, P. (2010). Potassium deficiency induces the biosynthesis of oxylipins and glucosinolates in Arabidopsis thaliana. BMC Plant Biology 10: 172.