Professor Andy Lovering

Supervisor Details

Contact Details

Professor Andy Lovering

School of Biosciences, University of Birmingham

Scientific Background

Research Interests

We take on a variety of projects, but typical areas include:

Invasion – how are prey cells recognized, and how do predators breach the outer membrane? This is a multifactorial process – no genetic resistance to predation has ever been observed (in contrast to bacteriophages and their receptors, which are subject to a relatively rapid development of resistance).
Protection – what factors prevent Bdellovibrio from killing itself? We published the first such example of a predator self-immunity protein in 2015 (an interesting case of evolution shaping one protein to block two enzymes): Nature Commun. 2015 Dec 2;6:8884.
Signalling – what are the stimuli that govern switching between the different lifecycle stages (swim > recognition > adhere > enter > metabolize > divide > exit)? Some of these pathways utilize the second messenger cyclic-di-GMP (common to many bacteria, but used herein to regulate predation).
Metabolism – predators are very distinct, often losing pathways for amino acid and vitamin biosynthesis, but encoding a massive array of novel proteases, lipases, nucleases and transporters.
Motility – prey density is high in biofilms; predators can exploit this by using a cryptic form of motility (“smooth gliding” – that pushes the cell over surfaces, utilizing a motor that runs on a helical thread around the cell periphery).

Research Groups

Structural and Molecular Cell Biology

Supervision Style

In three words or phrases: Encouraging, enthusiastic, aim to inspire.

Provision of Training

We aim to provide training that allows a full grasp of the path from gene to structure to function; students become proficient at structural biology, with additional skills that can be project-specific (e.g. assays for enzymatic projects, protein complexes for signalling projects, investigative biochemistry for projects of novel function).

Progression Monitoring and Management

I expect the group to support, develop and converse as a team, and to take interest in the breadth of what we study. Management comes from me as team lead, and progression results from a combination of self-drive and co-operative decision making.

Communication

This is largely at the students discretion, in the style that suits them best. As a group, we do a lot of idea/result discussion as informal conversation, and hold more standard one-on-one meetings if there is more intricate planning to be done. Science is ultimately a mixture of fun (new results) within the context of something more formal (student career progression), and we aim to keep a good balance throughout.

PhD Students can expect scheduled meetings with me:

In a group meeting

At least once per fortnight

In year 1 of PhD study

At least once per fortnight

In year 2 of PhD study

At least once per fortnight

In year 3 of PhD study

At least once per fortnight

These meetings will be mainly face to face, and I am usually contactable for an instant response 3 or 4 days a week.

Working Pattern

Certain tasks in my lab need to occur at set times, and students need to be able to commit to a rota/timetable shared with other members of the team.

Notice Period for Feedback

I need at least 1 week’s notice to provide feedback on written work of up to 5000 words.

Project Details

Professor Andy Lovering is the supervisor on the below project:

Structure & Function of Predatory Bacteria Surface Recognition

Secondary Supervisor(s): Dr Patrick Moynihan

University of Registration: University of Birmingham

BBSRC Research Themes:

Sustainable Agriculture and Food (Microbial Food Safety)
Understanding the Rules of Life (Microbiology, Structural Biology)

No longer accepting applications

Project Outline

The bacterial predator Bdellovibrio bacteriovorusis a natural killer of other bacteria (in water treatment, food security, environmental bioremediation & healthcare, (1,2). It would thus be beneficial if we understood the molecular basis of its predatory lifestyle, and the “toolkit” encoded to manipulate (and eventually destroy) the prey cell (2). The staged lifecycle of predation is fascinating – the predator locating and entering the prey cell, metabolizing it from within, and then bursting out to begin the cycle anew.

The Lovering lab specializes in structure:function:mechanism relationships, and the basis of this project will be taking a select grouping of receptor genes whose features (lipidation, beta-propeller fold) are suggestive of being presented at the predator:prey interface for tight recognition. Structural biology will detail the interaction interfaces involved, and unbiased (phage display) screens will identify the peptides capable of binding these receptors. Our goal is to uncover specificity determinants that allow us to understand how Bdellovibrio can kill large numbers of vastly different strains, eventually leading to the engineering of new bespoke predators.

An overview of our approach can be seen here: https://www.youtube.com/watch?v=FioNZppFlKY, and good examples of discerning predatory function via structure can be taken from two of our recent publications (3, 4). Structure is particularly important because Bdellovibriois unique and shares limited sequence homology with “traditionally well-characterized” bacteria. For example, our first clues into exit recently resulted in the discovery of a novel lysozyme that recognizes a chemical marker which Bdellovibrio uses to signify prey wall as different to self (5).

There are many other potential “secrets” to uncover about prey recognition, and this project will develop new ideas to investigate as it progresses.

References

https://www.news-medical.net/news/20230619/Predatory-bacteria-could-be-used-to-purify-water-in-the-future-study-suggests.aspx
Caulton SG, Lovering AL. Bacterial invasion and killing by predatory Bdellovibrio primed by predator prey cell recognition and self protection. Curr Opin Microbiol. 2020.https://www.sciencedirect.com/science/article/pii/S1369527420300837?via%3Dihub
Harding CJ, Cadby IT, Moynihan PJ, Lovering AL. A rotary mechanism for allostery in bacterial hybrid malic enzymes. Nature Communications. 2021.https://www.nature.com/articles/s41467-021-21528-2
Meek R, Cadby IT, Moynihan, PJ, Lovering AL. Structural Basis for Activation of a Bdellovibrio Diguanylate Cyclase that Licenses Prey Entry. Nature Communications2019.https://www.nature.com/articles/s41467-019-12051-6
Harding CJ, Huwiler SG, Somers H, Lambert C, Ray LJ, Till R, Taylor G, Moynihan PJ, Sockett RE, Lovering AL. A Lysozyme with Altered Substrate Specificity Facilitates Prey Cell Exit by the Periplasmic Predator Bdellovibrio bacteriovorus. Nature Communications2020.https://www.nature.com/articles/s41467-020-18139-8

Techniques

Molecular Biology (chiefly cloning, mutagenesis).
Protein expression & purification.
Protein crystallization.
Structure Determination.
X-Ray Crystallography.
Protein function/analysis.
Enzyme Assays.
Biophysical methods (AUC, SAXS, ITC, microscale thermophoresis).
Bioinformatics.