Aggregation of Polyglutamine Tracts Driven by httNT α-helices

Huntington is a lethal inherited disease with symptoms of the cognitive and psychiatric disorder. It is the most common form of polyglutamine aggregation related diseases. At a molecular level, the disease is associated with the aggregation of polyglutamine tracts resulting from the heavy enzymatic cleavage of Huntingtin. The seventeen amino acid httNT segment, attached to the N-terminal of polyglutamine tract, has a slight tendency towards α-helix structure and is believed to be playing an important role in the aggregation of polyglutamine tracts. In comparison to the dominant β-strand templated protein aggregation mechanism, the α-helix driven aggregation is not commonly seen.

In this project, our primary goal is to use both all-atom and coarse-grained molecular dynamics simulations to test the validity of httNT driven aggregation mechanism of polyglutamine tracts which is based on the current experimental findings. The project will involve both simulations with currently available models and also aim to develop new coarse-grained models which can capture the conformational dynamics and flexibility of the underlying system.

Postdoctoral Researcher:
Applicants should have a Ph.D. in physics, physical chemistry, material science, chemical engineering, or a related field. Prior experience in the field of theory or simulations of soft/biological matter will be an advantage. Applications must include the following documents.
- CV
- Summary of past research
- Statement of research interests
- Contact details of at least 2 scientific referees