Searching for amyloid forming bacteria using bioinformatics and experimental approaches

Description

Amyloid proteins are biologically fascinating, with many aspects of their formation and interaction poorly understood, and are intimately involved in a variety of human diseases. Typically regarded as the result of pathological misfolding, for some proteins (mainly bacterial proteins) amyloid is the normal functional structure. Recent work shows that these proteins, found on the surface of gut bacteria, can interact with host proteins that are also capable of (mis)folding into an amyloid state with potential relevance for conditions such as Parkinson’s and Alzheimer’s diseases. At present, only a few bacterial functional amyloid proteins have been characterised and much remains poorly understood about their interaction with host proteins. This project aims to discover new families of bacterial function amyloid proteins and probe their interaction with host proteins, cells and systems.

Bacterial functional amyloid proteins adopt a B-helical structure and are built of repeating sequences with each repeat contributing a number of layers of the B-helix. The bioinformatics discovery phase of the project therefore centres on revealing unsuspected repeat proteins, then deploying state of the art ab initio structure prediction methods, as exemplified by Google AlphaFold, to test whether they adopt a B-helical structure. These methods have made huge advances in recent years and have broad applicability across the protein universe: the successful applicant will therefore gain hugely valuable experience in this fast-moving area.

Following identification of potential candidate proteins will be recombinantly expressed and ability to form amyloid and interactions with host proteins assessed using a range of experimental techniques. Effect of microbial proteins on cell biological function will be probed at the second institution by studying the effect on cell signalling pathways in smooth muscle and endothelial cells.

This project will provide training in biochemical and biophysical techniques and cell signalling to complement novel bioinformatics skills. The aims of this project are to enhance understanding of the interactions between bacterial and host proteins, along with increased knowledge of the process and impact of novel structural re-arrangements that can occur upon protein-protein interaction. This knowledge has the potential to understand the role of potentially pathogenic bacteria introduced via the gut microbiome or infection in a range of health and disease situations.

Informal enquiries may be made to 

HOW TO APPLY

Applications should be made by emailing  with a CV and a covering letter, including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project/s and at the selected University. Applications not meeting these criteria will be rejected. We will also require electronic copies of your degree certificates and transcripts.

In addition to the CV and covering letter, please email a completed copy of the NLD BBSRC DTP Studentship Application Details Form (Word document) to , noting the additional details that are required for your application which are listed in this form. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.

Availability

Open to students worldwide

Funding information

Funded studentship

Studentships are funded by the Biotechnology and Biological Sciences Research Council (BBSRC) for 4 years. Funding will cover tuition fees at the UK rate only, a Research Training and Support Grant (RTSG) and stipend. We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

Supervisors

References

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