EPSRC DTP PhD studentship: Detecting and Modelling Signals from Single Biomolecules and their Networks

Location: University of Exeter, Streatham Campus, Exeter, Devon

Project Description:
This project will develop an optical technique that is capable of directly monitoring interaction kinetics and structural changes of individual proteins. Currently available techniques can only track the motion of protein or its moieties when the protein is chemically modified, i.e. attached to a chemical label. Without the need of a label, this optical technique will provide a universal tool for the unabated exploration of protein kinetics and structural changes of individual proteins.
Kinetic and conformational dynamics of proteins that are part of a network give rise to particular functions such as signalling. These signalling events will be investigated in in vitro networks, composed of polymerases and nucleic acids, or receptor molecules and their ligands. The biomolecular network is ultimately investigated in whole-cell extracts, to mimic the physiological response of a cell. This approach establishes a novel platform for synthetic biology.

The student will design and build dedicated optical biosensor setup based on platform technology advanced in Prof. Vollmer’s laboratory. Student will further establish microfluidics and temperature control capabilities. Student will then develop hardware and software capabilities to acquire single molecule data streams at a high time resolution. The response of a network composed of several interacting biomolecules will be recorded by detecting constituents at the single molecule level [1]. Student will develop a theoretical approach (Prof. Terry, Dr. Walker) to analyse experimental data. Mathematical capabilities will be developed to identify the specific signal associated with the dynamics of individual proteins and their conformational (shape) changes. Deciphering these specific signalling events will require novel mathematical tools for analysis of a complex data streams, akin to methods in electrophysiology and neuroscience (Prof. Terry, Dr. Walker). Overall, student will establish a novel approach to synthetic biology, enabling the read-out of complex network dynamics by monitoring specific signalling events from biomolecules interacting with or at an optical biosensor interface.

The project will be completed in the given timeframe of the funding period (3.5 years). Student will train on optics and optical methods for biodetection. Student will acquire knowledge in quantitative analysis of biological systems. Student will train on mathematical analysis of optical biosensor data. Student will benefit from close mentoring by all three supervisors and state-of-the-art laboratory facilities available at the Living Systems Institute.
[1] Vollmer et.al. “Ultraspecific and highly sensitive nucleic acid detection by integrating a DNA catalytic network with a label-free microcavity” Small (2014).