Coventry University Featured PhD Programmes
Imperial College London Featured PhD Programmes
The Francis Crick Institute Featured PhD Programmes
Norwich Research Park Featured PhD Programmes
Cardiff University Featured PhD Programmes

Dynamics of protein folding on the ribosome

  • Full or part time
    Dr D Balchin
  • Application Deadline
    Tuesday, November 12, 2019
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

This 4-year PhD studentship is offered in Dr David Balchin’s Group based at the Francis Crick Institute (the Crick).

Proteins are synthesised on the ribosome as linear polypeptides that in most cases must fold into defined 3-D structures to be biologically active. How this occurs is a fundamental problem in biology. Although few proteins fold efficiently in a test tube, in vitro studies of isolated model proteins underpin our current understanding of the folding process. Folding in vivo is a much more sophisticated operation. Cells employ a complex network of protein biogenesis factors that stimulate folding reactions, reverse misfolding, and inhibit aggregation [1]. Failure of the cellular protein folding machinery has severe consequences. Protein misfolding is a hallmark of neurodegenerative disease, cystic fibrosis and type II diabetes, and a key contributor to the process of aging [2].

The overarching goal of our lab is to understand protein biogenesis in molecular detail. To do this, we take a bottom-up approach. We reconstitute cellular protein synthesis and folding networks in vitro, and use a range of biochemical, biophysical and structural approaches to characterize dynamic folding intermediates [3]. By bridging the gap between in vitro and in vivo concepts of protein folding, we also hope to understand the molecular principles underlying protein misfolding diseases in humans.

This project will explore how a protein’s folding pathway is coupled to its synthesis at the ribosome. It is now appreciated that proteins begin to fold during translation, even before their synthesis is complete. “Co-translational” folding is the first step in the biogenesis of all proteins in the cell, and can have a profound influence on protein structure and function [4]. However, the underlying mechanisms are not known. To address this, we are developing new ways to probe the conformational dynamics of proteins during translation. The project will combine hydrogen/deuterium exchange-mass spectrometry, chemical crosslinking and FRET to follow the folding of a nascent protein on the ribosome. Future directions will include investigating the influence of translation rate, domain topology, and ribosome-associated chaperone proteins on folding.

Candidates should have a degree in Biochemistry, Molecular Biology, or a related subject. Familiarity with basic molecular biology techniques, and experience with recombinant protein expression and purification would be advantageous. This project would particularly suit candidates with a background in protein biochemistry, and an interest in protein folding, structure and dynamics.

equivalent in a relevant subject and have appropriate research experience as part of, or outside of, a university degree course and/or a Masters degree in a relevant subject.


Funding Notes

Successful applicants will be awarded a non-taxable annual stipend of £22,000 plus payment of university tuition fees. Students of all nationalities are eligible to apply.


1. Balchin, D., Hayer-Hartl, M. and Hartl, F. U. (2016)
In vivo aspects of protein folding and quality control.
Science 353: aac4354. PubMed abstract
2. Chiti, F. and Dobson, C. M. (2017)
Protein misfolding, amyloid formation, and human disease: A summary of progress over the last decade.
Annual Review of Biochemistry 86: 27-68. PubMed abstract
3. Balchin, D., Miličić, G., Strauss, M., Hayer-Hartl, M. and Hartl, F. U. (2018)
Pathway of actin folding directed by the eukaryotic chaperonin TRiC.
Cell 174: 1507-1521 e1516. PubMed abstract
4. Thommen, M., Holtkamp, W. and Rodnina, M. V. (2017)
Co-translational protein folding: progress and methods.
Current Opinion in Structural Biology 42: 83-89. PubMed abstract

FindAPhD. Copyright 2005-2019
All rights reserved.