EASTBIO Elucidating the mechanism of pathogen clearance in fungal infections using biologics tools targeting cell surface proteins.

Supervisors:

Professor Carol Munro (University of Aberdeen)
https://www.abdn.ac.uk/ims/profiles/c.a.munro

Dr Daan van Aalten (University of Dundee)
https://www.sites.google.com/site/vanaaltenlab

Dr Soumya Palliyil (University of Aberdeen)
https://www.abdn.ac.uk/people/soumya.palliyil

Virulence factors are expressed on the fungal cell surface which plays a major role in pathogen:host interactions. In a targeted approach we have isolated recombinant monoclonal antibodies that recognise surface proteins of fungal pathogens with a focus on Candida and Aspergillus species that cause life-threatening invasive fungal infections. These antibodies have huge potential as novel theranostics, to accurately diagnose and treat fungal infections including those caused by multi-drug resistant fungal species. Indeed the risk of developing a severe fungal lung infection is heightened in patients with influenza and Covid-19.

This PhD project will extensively characterise the binding interactions of our lead theranostic candidates using heterologously expressed cell surface proteins, short peptide sequences, and a collection of wild type fungal cells and clinical isolates. At the University of Dundee, the Van Aalten lab has elucidated the structure of several fungal-specific cell surface proteins and will provide expertise in the expression of fungal glycoproteins that will be utilised for the characterisation of antibody binding using biochemical assays (ELISAs) and Surface Plasmon Resonance (SPR). In addition, they can provide expertise in protein crystallography to elicit antibody binding to the fungal targets and in silico construction of the 3D structure of these antibodies and target proteins to study the macromolecular interactions through interface predictions and molecular docking. The student will also receive advanced training in antibody engineering by being part of the Scottish Biologics Facility, headed by Dr Soumya Palliyil. Using the latest tools in protein engineering and combining the expertise of recombinant antibody development, this project will also explore the feasibility of generating bispecific formats of the existing antibodies e.g. two different antigen binding arms on the same antibody molecule or potent antibody drug conjugates (ADCs) by biochemically coupling an antimicrobial agent to the selected lead antibody for enhanced pathogen killing.

Application Procedure:

http://www.eastscotbiodtp.ac.uk/how-apply-0

Please send your completed EASTBIO application form, along with academic transcripts to Alison McLeod at [Email Address Removed]. Two references should be provided by the deadline using the EASTBIO reference form. Please advise your referees to return the reference form to [Email Address Removed].