Professor Andy Wilson

Supervisor Details

Contact Details

School of Chemistry, University of Birmingham

Scientific Background

Research Interests

The Wilson group are interested in the application of synthetic molecules to problems in Chemical Biology and Materials Science. We pursue both curiosity driven fundamental research and mission inspired research addressing societal challenges. The group is currently supported by The University of Birmingham, EPSRC and BBSRC. Our group is participating in several large-scale, multi-investigator programmes including SPIDR, a major BBSRC investment, and led on the EPSRC PoPPI Programme.

Scientific Inspiration

I don’t have a sole scientific inspiration – they are in so many places. My supervisors – David Leigh FRS, Andy Hamilton FRS and Bert Meijer, my other mentors, collaborators, current and former co-workers!

Research Groups

Wilson Research Group

SPIDR

POPPI

Supervision Style

In three words or phrases: outcome-oriented, supportive and tailored.

Provision of Training

I endeavour to provide an environment where myself alongside experienced PhD and postdoctoral coworkers can support and encourage training in technical and complementary skills. Our aim is to foster the confidence and independence to take on new research techniques and explore new research concepts.

Progression Monitoring and Management

I find it useful to formally review progress (usually) on a monthly basis with a short report submitted in advance, which allows us both to prepare and think about how to troubleshoot any problems and/or prioritise next steps. At the same time, I like to chat informally on a regular basis and will come into lab to see how things are going on most days. Ultimately, we need a structure that allows you to be the one tell me “what we should do next” by the end of your PhD.

Communication

The group make use of TEAMS for general messaging and I like to be around lab for informal discussion. I might share information with the group and will often respond to e-mail outside normal working hours, but I do not expect you to do the same and am keen to support a work/life balance that works for you.

PhD Students can expect scheduled meetings with me:

In a group meeting

At least once a fortnight

In year 1 of PhD study

At least once a month

In year 2 of PhD study

At least once a month

In year 3 of PhD study

At least once a month

These meetings will be mainly face to face, and I am usually contactable for an instant response on every working day.

Working Patterns

The timing of work in my lab is completely flexible, and (other than attending pre-arranged meetings), I expect students to manage their own time.

Notice Period for Feedback

I need at least 2 weeks' notice to provide feedback on written work of up to 5000 words.

MIBTP Project Details

Current Projects (2025-26)

Primary supervisor for:

Development of Peptidomimetic Tools to Understand and Modulate the Function of Bacterial Outer Membrane Proteins

See the PhD Opportunities section to see if this project is currently open for applications via MIBTP.

Please Note: The main page lists projects via BBSRC Research Theme(s) quoted and then relevant Topic(s).

Development of Peptidomimetic Tools to Understand and Modulate the Function of Bacterial Outer Membrane Proteins

Secondary Supervisor(s): Dr Tim Knowles

University of Registration: University of Birmingham

BBSRC Research Themes: Understanding the Rules of Life (Structural Biology)

Project Outline

The rise of antibiotic-resistant bacteria poses a significant and escalating global threat, demanding new approaches and targets to fight infections. This issue is particularly critical with Gram-negative bacteria, as there are very few antibiotics in development, and new options for clinical use are unlikely to emerge soon.

Gram-negative bacteria are generally more resistant to antibiotics than Gram-positive bacteria due to their complex cell envelope structure, which includes an additional outer membrane (OM). This outer membrane has a unique lipid arrangement, with lipopolysaccharides (LPS) on the outer layer and phospholipids on the inner layer, providing enhanced protection. It acts as a barrier to hydrophilic molecules and slows the penetration of small hydrophobic molecules, contributing to their higher resistance to hydrophobic antibiotics and detergents.

The proteins embedded in the outer membrane are central to microbial defense, playing critical roles in pathogenesis, virulence, and multidrug resistance. These outer membrane proteins (OMPs) are involved in key processes driving infection and disease progression, and they are vital for maintaining cellular homeostasis by allowing the excretion of toxic substances, like antibiotics, and the uptake of nutrients.

Given the outer membrane's importance, understanding its biogenesis is essential both as a fundamental biological process and as a potential avenue for developing new antibiotic targets.

The Maintenance of outer membrane Lipid Asymmetry (Mla) pathway is a multicomponent system found in all gram-negative bacteria that contributes to virulence, vesicle blebbing and preservation of the outer membrane barrier function. It acts by maintaining outer membrane asymmetry by removing ectopic lipids from the outer leaflet of the outer membrane and returning them to the inner membrane through three proteinaceous assemblies. The MlaA-OmpC complex, situated within the outer membrane; the periplasmic phospholipid shuttle protein, MlaC; and the inner membrane ABC transporter complex, MlaFEDB.

Building on our expertise in developing peptidomimetic inhibitors of protein-protein interactions1-3 this project focuses on developing candidate ligands that mimic (i) the OM lipoprotein MlaA and potentiate its interaction with OmpC.4 (ii) the OM lipoproteins MlaC and MlaD to inhibit their protein-protein interactions.5 This will be complemented by development of chemical probes of these peptidomimetics for phospholipid binding that can exploit the rapid and non-specific labelling of diazirines.6 Such reagents will allow us to assess the consequence of protein-protein interaction inhibition on ligand binding and localization. Collectively these chemical probes will represent unique tools to modulate protein-protein interactions involved in OM biogenesis allowing us to understand their functional role and provide starting points for development of new antimicrobial mitigations.

References

1. R. S. Dawber, D. Gimenez, M. Batchelor, J. A. Miles, M. H. Wright, R. Bayliss and A. J. Wilson, ChemBioChem, 2024, 25, e202300649.

2. E. E. Cawood, E. Baker, T. A. Edwards, D. N. Woolfson, T. K. Karamanos and A. J. Wilson, Chem. Sci., 2024, DOI: 10.1039/D4SC02240H.

3. F. Hóbor, Z. Hegedüs, A. A. Ibarra, V. L. Petrovicz, G. J. Bartlett, R. B. Sessions, A. J. Wilson and T. A. Edwards, RSC. Chem. Biol., 2022, 3, 592-603.

4. J. Abellón-Ruiz, S. S. Kaptan, A. Baslé, B. Claudi, D. Bumann, U. Kleinekathöfer and B. van den Berg, Nature Microbiology, 2017, 2, 1616-1623.

5. P. Wotherspoon, H. Johnston, D. J. Hardy, R. Holyfield, S. Bui, G. Ratkevičiūtė, P. Sridhar, J. Colburn, C. B. Wilson, A. Colyer, B. F. Cooper, J. A. Bryant, G. W. Hughes, P. J. Stansfeld, J. R. C. Bergeron and T. J. Knowles, Nat. Commun., 2024, 15, 6394.

6. J. E. Horne, M. Walko, A. N. Calabrese, M. A. Levenstein, D. J. Brockwell, N. Kapur, A. J. Wilson and S. E. Radford, Angew. Chem. Int. Ed., 2018, 57, 16688-16692.

Development of Organelle Targeted Ligands to Delineate GPCR signalling

See the PhD Opportunities section to see if this project is currently open for applications via MIBTP.

Please Note: The main page lists projects via BBSRC Research Theme(s) quoted and then relevant Topic(s).

Development of Organelle Targeted Ligands to Delineate GPCR signalling

Secondary Supervisor(s): Professor Davide Calebiro

University of Registration: University of Birmingham

BBSRC Research Themes: Understanding the Rules of Life (Structural Biology)

Project Outline

G protein-coupled receptors (GPCRs) are a large family of integral membrane proteins comprising seven transmembrane α-helical domains that relay extracellular signals to the interior of the cell. GPCRs are involved in multiple physiological process including cell growth, neurotransmission, metabolism & immune response; they can misfunction in disease and consequently have served as fertile targets for drug discovery and development (approx. 30% of all drugs target this family). Extensive research has characterized GPCR signalling at the cell surface, however more recent studies pioneered by our team using advanced microscopy methods have established that GPCRs can signal from multiple intracellular compartments such as early endosomes or the Golgi.1, 2 Such intracellular signalling can have distinct effects from cell-surface signalling, even when the same effectors and second messengers are activated. However, delineating the function of specific GPCRs in distinct organelles is difficult. This project will develop and harness state of the art chemical biology tools and advanced optical methods to control and monitor GPCR signalling in space and time and evaluate the functional consequences of GPCR signalling from intracellular compartments. The project will benefit from access to the state-of-the-art expertise and facilities for advanced microscopy of the Centre of membrane Proteins and Receptors (COMPARE).3 We will focus on FFA44 and NTSR1 as model GPCRs. Building on our groups expertise in development of covalent chemical probes5 and protein labelling methods,6 a range of small-molecule agonists/antagonists will be armed with: (i) organelle localization sequences, (ii) light/enzyme responsive uncaging groups (iii) photoswitchable groups and (iv) covalent warheads for conjugation to organelle specific protein fusions with Halo/Snap-Tag.7 This will facilitate spatiotemporally controlled agonism/antagonism of the target GPCRs, in that a range of tools will be developed to either localize to a specific organelle (e.g. early endosomes) or, can be activated in the target organelle to exert their affect upon their target GPCR. These powerful tools will thus allow us to dissect out the functional significance of specific intracellular GPCR signalling events and separate these from cell surface signalling, which could pave the way to a new generation of more selective and better tolerated drugs

References

1. D. Calebiro, European Journal of Endocrinology, 2021, 184, R41-R49.

2. D. Calebiro, V. O. Nikolaev, M. C. Gagliani, T. de Filippis, C. Dees, C. Tacchetti, L. Persani and M. J. Lohse, PLoS Biol., 2009, 7, e1000172.

3. J. Grimes, Z. Koszegi, Y. Lanoiselée, T. Miljus, S. L. O’Brien, T. M. Stepniewski, B. Medel-Lacruz, M. Baidya, M. Makarova, R. Mistry, J. Goulding, J. Drube, C. Hoffmann, D. M. Owen, A. K. Shukla, J. Selent, S. J. Hill and D. Calebiro, Cell, 2023, 186, 2238-2255.e2220.

4. E. Tripp, S. L. O’Brien, G. Smith, A. Boufersaoui, J. Roberts, J. Pike, J. Correia, T. Miljus, D. A. Tennant, B. D. Hudson, G. Milligan, Z. Gerhart-Hines, T. W. Schwartz and D. Calebiro, bioRxiv, 2023, DOI: 10.1101/2023.07.28.550805, 2023.2007.2028.550805.

5. T. Ueda, T. Tamura, M. Kawano, K. Shiono, F. Hobor, A. J. Wilson and I. Hamachi, J. Am. Chem. Soc., 2021, 143, 4766-4774.

6. J. E. Horne, M. Walko, A. N. Calabrese, M. A. Levenstein, D. J. Brockwell, N. Kapur, A. J. Wilson and S. E. Radford, Angew. Chem. Int. Ed., 2018, 57, 16688-16692.

7. G. V. Los, L. P. Encell, M. G. McDougall, D. D. Hartzell, N. Karassina, C. Zimprich, M. G. Wood, R. Learish, R. F. Ohana, M. Urh, D. Simpson, J. Mendez, K. Zimmerman, P. Otto, G. Vidugiris, J. Zhu, A. Darzins, D. H. Klaubert, R. F. Bulleit and K. V. Wood, ACS Chem. Biol., 2008, 3, 373-382.

Co-supervisor on projects with Professor Aga Gambus and Professor Teresa Carlomagno.

Previous Projects (2024-25)

Primary supervisor for:

Development and Application of Chemical Probes to target Protein-Protein Interactions