PDRA positions

We will shortly be recruiting a fixed-term PDRA position funded by the BBSRC to explore the earliest processes in polypeptide self-assembly using mass spectrometry methods. Please contact me for further details, or watch this space.

PhD positions:

PhD opportunities are regularly available within my group. Please contact me for further details.

Senior Honours Projects:

I typically offer two Senior Honours Projects (one in Semester 1, one in Semester 2). One of these projects may be adapted to suit Chemical Physics students, please contact me for further details.

Nucleation of self-assembly in peptide systems

with Dr Perdita Barran, School of Chemistry

Aberrant self-assembly of proteins and polypeptides into nanoscale fibrils is linked to diseases like Alzheimer’s Disease and adult-onset diabetes. Outside the body, it appears that fibrillar self-assembly is a fundamental property of the polypeptide chain, possibly representing the lowest energy state of all proteins. Although we understand increasing amounts about how these structures are formed and what they look like, the initial events that trigger self-assembly remain beyond our grasp. We know that fibril assembly is a nucleated process, and that addition of pre-formed nuclei dramatically accelerates aggregation. The project will use mass spectrometry combined with molecular dynamics simulation to explore the early events in the nucleation of amyloid-like fibrils in simple polypeptide systems.

Proteins as model colloids: mapping the phase diagram of ovalbumin and bovine serum albumin

The protein ovalbumin is the main constituent of egg white. Under conditions of low salt, moderate pH and high temperatures, ovalbumin aggregates to form a turbid and brittle gel, familiar to anyone who has boiled an egg. Under conditions of high salt and high temperature, the protein instead forms a transparent and elastic gel. A similar gel is formed at room temperature when the protein is exposed to extreme pH values. This project will map out the density/pH phase diagram of ovalbumin and bovine serum albumin gelation using optical spectroscopic methods.

MSc project

Nucleation in Biological Systems

Dr Cait MacPhee (with Dr. Rosalind Allen)

A quick glance at wikipedia suggests that “nucleation” is a physical process involving the onset of crystal formation in a supersaturated liquid. The same term is also commonly applied to the mechanism underlying the onset of protein self-assembly and aggregation in biological systems. Such self-assembly and aggregation is of interest as it underlies a range of human and animal disorders such as “Mad Cow Disease” and the human equivalent Creutzfeldt-Jacob Disease, as well as adult-onset diabetes. But is this initiation of aggregation really “nucleation” in the classical sense, and can we make sense of it in the inherently messy environment of biology?

You will look at nucleation of protein aggregation using a model protein system. This project will involve using high through-put fluorescence methods to perform (concurrently) the large number of identical experiments required to obtain the good statistics necessary to recognise and analyse rare events. You will also use simple fitting and modelling packages to extract the maximum meaningful information from this data set. Your results will be compared with existing data obtained for another protein, and you will help to develop a robust and general model of “nucleation” in these systems.

For further information, see:

Chiti et al (2006) Ann Rev Biochem 75: 333-366

Auer et al. (2008) Phys Rev Lett 101: 258101

Tessier and Lindquist (2007) Nature 447: 556-