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Biomimetic peptides to manipulate cell signalling responses

Principal Supervisor: Dr Jose Gutierrez-Marcos, School of Life Sciences and Dr. Jozef Lewandowski, Chemistry Department

PhD project title: Biomimetic peptides to manipulate cell signalling responses

University of Registration: University of Warwick

Project outline:

Although much is known about the role of non-peptide hormones in regulating growth and development in animals and plants, relatively little is known about the significant role played by small signalling peptides in regulating such processes. Recently, an increasingly large number of genes encoding small, secreted peptides in animals and plants have been implicated in mediating cell–cell interactions. For example, there are demonstrated roles for peptide signals in defence responses, cell proliferation and differentiation, maintenance of stem cell identity, and in reproduction. Although both genetic and biochemical methods have thus far been used to identify and characterise such peptides, we remain ignorant of their biophysical properties and how their physical structure relates to function and performance. This project aims to establish a link between the physical and chemical properties of a group of newly identified peptide ligands that regulate cell signalling developmental responses in plants and to engineer synthetic peptides with novel biological functions.

Key experimental skills involved:

The student will carry out a series of experiments designed to determine the peptide structure and the interactions with transmembrane receptors. NMR will be used to determine protein size, shape and oligomeric state for any SCR oligomers and complexes formed. These methods could also provide information of the dynamics of these proteins and their interactions with other key ligands and proteins. Complementing these techniques, synthetic design of peptide ligands and receptors will be employed for in vivo and in vitro functional assays.

References:

  1. Lewandowski, J.R., Halse, M.E., Blackledge, M., Emsley, L. (2015) Direct observation of hierarchical protein dynamics, Science 348 (6234): 578-581
  2. L. M. Costa, E. Marshall, M. Tesfaye, K. A. T. Silverstein, M. Mori, Y. Umetsu, S. L. Otterbach, R. Papareddy, H. G. Dickinson, K. Boutiller, K. A. VandenBosch, S. Ohki, J. F. Gutierrez-Marcos (2014) Central Cell-Derived Peptides Regulate Early Embryo Patterning in Flowering Plants, Science, 3244 (6180): 168-172

BBSRC Strategic Research Priority: Food Security and Molecules, Cells and Systems

Techniques that will be undertaken during the project:

The student will be working in a multidisciplinary environment: the laboratory of JGM has an international track record in peptide signalling in plants and the group of JL has an international track record in NMR analysis of protein structure. 

Contact: Dr Jose Gutierrez Marcos, University of Warwick