PARP inhibitors as novel crop protection agents

Supervisors: Dr Stephen A Rolfe, Professor Joe Harrity, Professor Julie Gray and Dr Stephen Lindell (Bayer CropScience AG)

BBSRC Industrial CASE Studentship

New crop protection agents that increase the tolerance of plants to abiotic stress could lead to significant increases in worldwide food production at a time when global warming and population increases threaten food security. Recently, it has been found that reducing the activity of plant ADP-ribose polymerases (PARPs) increases their ability to cope with abiotic stress. Bayer CropScience has developed small molecule PARP inhibitors that enhance plant stress tolerance resulting in improved growth and yield.

The aim of this project is to develop the next generation of PARP inhibitors by exploiting novel small molecule synthesis techniques to create new precursors to these compounds and related analogues. Plant imaging techniques (chlorophyll fluorescence and thermal imaging) will be used to develop a rapid, non-invasive screen to quantify plant responses to abiotic stress and then identify effective PARP inhibitors that increase stress tolerance. Initial studies will use an existing panel of PARP inhibitors produced by Bayer CropScience and the Harrity group. Once the characteristics of effective PARP inhibitors have been identified, the student will undertake an industrial placement at the Bayer lead generation facility (Frankfurt). They will generate arrays of new compounds for further testing leading to the production of a second generation of PARP inhibitors. This chemical and biological knowledge will be integrated to aid the rationale design of novel PARP inhibitors and improve our understanding of the relationship between PARPs and plant responses to stress.

The supervisory team consists of Prof Harrity who has expertise in generating new PARP inhibitor compounds, Dr Rolfe and Prof Gray who have expertise in imaging plant responses to stresses and PARP biology and Dr Lindell at Bayer CropScience who will provide an industrial perspective on the project goals and ambitions. The student, who ideally will have a background in biochemistry or chemistry with an interest in plant biology, will register for a PhD in the Department of Animal and Plant Sciences, University of Sheffield and enrol in the University-wide Doctoral Development Programme.

If you are interested please visit our website at www.sheffield.ac.uk/aps or contact s.rolfe@sheffield.ac.uk or apply directly online at www.sheffield.ac.uk/postgraduate/research/apply

The studentship is for 48 months and is open to UK/EU citizens, according to BBSRC guidelines.