Professor Andrew Lovering

Professor Andrew Lovering

School of Biosciences
Professor of Structural Biology

Contact details

Address
704, School of Biosciences
The University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom

Andrew Lovering is a Professor of Structural Biology here at Birmingham, and his research interests involve utilising structural biology and complementary techniques to investigate protein function – many of these projects involve the unusual Bdellovibrio, an amazing bacterial predator of other bacteria.

Bacterial predators are fascinating organisms that may find general usage as 'living antibacterials'. His lab is chiefly concerned with understanding the tools they use to kill other bacteria and how they regulate the various stages of their unusual lifecycle (also take a look at “research” tab). Approximately a third of the genome from the model predator Bdellovibrio bacteriovorus encodes for proteins with no discernible homology to those from other (non-predatory) bacteria; this makes structural methods ideal for investigating function. He studies these predatory enzymes and protein complexes in-vitro, collaborating to tie function in with in-vivo context. Essentially, the goal of the lab is using structural detail to find new exciting biology.

The figure below demonstrates the staged lifecycle of Bdellovibrio, annotated with a select few of the structures the group have solved.

Staged lifecycle of Bdellovibrio

1.Bdellovibrio lifecycle. 2.Hexameric hub for prey material assimilation. 3.Pentameric outer membrane protein (contrary to most bacterial trimeric OMPs, see below). 4.Prey recognition fibre. 5.Immunity protein (pink) prevents predator self-lysis from toxin (blue). 6.Hollow “coconut-shaped” transporter. 7.Electron density map. 8.Lattice-forming effector. 9.Cross section through a novel protein “tube”.

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

Invasion – how are prey cells recognized, and how do predators breach the outer membrane? This is a multifactorial process – no acquired/developed resistance to predation has ever been observed (in contrast to bacteriophages and their receptors, which are subject to a relatively rapid development of resistance). Discover how Bdellovibrio bacteriovorus targets a broad range of bacterial species.

Membrane protein complexityBdellovibrio and other undercharacterized bacteria have interesting lifestyles whose function requires membrane proteins that deviate from the templates seen in E. coli and other model organisms. We are very interested in how evolution has shaped these, often breaking established rules and expectations. Explore research on bacterial predator proteins and lipid trapping.

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). Learn more about the bacterial predation in Bdellovibrio.

Effectors – predators are very distinct, using a swathe of specialized enzymes to manipulate and assimilate prey. This area is very broad and includes turning a dead cell into a temporary home, incorporating host membranes, breaking down ribosomes, and even signalling to kin that you’re inside and they should find a different cell to invade! Read the study on bacterial predation and prey cell exit mechanisms.

Biography

Andrew grew up in Wales (Barry to be precise) and studied for both his undergraduate degree (Biochemistry) and PhD (structural biology of therapeutic enzymes) at the University of Birmingham, before beginning a 6 and a half year stint in Vancouver Canada. In his postdoctoral years he began to appreciate bacteria and the amazing diversity of mechanisms they utilize. In 2010 he came back to the UK to start his own group looking into how we can utilise a 'living antibiotic', the bacterium Bdellovibrio bacteriovorus, to tackle bacterial pathogens.

Recognition of our work has come from :

  • (2012) Presented with the ICAAC Young Microbiologist of the Year Award, administered by the American Society for Microbiology.
  • (2014-2017) Awarded prestigious EMBO Young Investigator status.
  • (2018-2023) Awarded Wellcome Investigator status.

Teaching

He teaches on several undergraduate and postgraduate modules, including Bio311 (antibiotic resistance component) and Bio305 (cell wall biosynthesis and staphylococcal & streptococcal disease topics).

Postgraduate supervision

UK students can apply via the MIBTP scheme, and non-UK students by the Darwin scheme – both normally take applications at the end of the calendar year for entry the following year, please email Professor Lovering if you have any questions.

Research

Structure: function relationships of bacterial proteins

His laboratory uses X-ray crystallography and cryoEM to study the molecular basis of protein function. They are interested in a variety of bacterial systems - especially those with the potential for antibiotic development. One of these systems involves analysis of the remarkable predatory bacterium Bdellovibrio bacteriovorus. Predatory bacteria feed off and eventually kill other bacteria, and thus research into this process has potential therapeutic possibilities. Bdellovibrio is the model predatory organism, and possesses an unusual lifestyle where it enters its prey through the outer membrane and resides in the periplasm. The host cell changes shape (forming a structure termed the "bdelloplast") and the Bdellovibrio cell grows and replicates using material obtained from prey breakdown. Progeny then exit the dead host to start the cycle anew.

They are using structural methods to study Bdellovibrio proteins with the aim of understanding the precise function of proteins involved in predation events and how Bdellovibrio responds to the challenges of intraperiplasmic growth.

Many of these proteins are unique to Bdellovibrio, and are thus termed part of the "predatosome". Of course, there is much more to study, not forgetting prey recognition events, membrane entry, bdelloplast formation, host material hydrolysis, predation on biofilms, motility, and signalling/regulation of all of the above!

We take a modern approach to structural biology, augmenting x-ray and cryoEM structure determination with informatics, protein design (including AI-led approaches such as artificial proteins to block function), evolutionary analysis and biophysical and biochemical characterization.

The laboratory has a number of other collaborations and projects ongoing, both within and external to Birmingham.

Bdellovibrio predation lifecycle

Figure 1: Bdellovibrio predation lifecycle

Other activities

We have a general interest in unusual microbes and unusual proteins – outside science Andy enjoys (in no particular order) time with family, Aston Villa, beer, professional wrestling, 80s movies, good grub, true crime documentaries, test cricket, snooker, puzzles and lab gene synthesis sweepstakes.

Publications

Recent publications

Article

Slope, LN, Shah, A, Taylor, MJ, Borghesani, V, Caulton, SG, Brooks, NJ, Hadley, KA, Rose, G, Hunter, RI, Mkami, HEL, Smith, GM, Leney, AC, Buurma, NJ, Lovering, AL, Lovett, JE & Peacock, AFA 2026, 'Design of a site selective heterochromic bimetallic lanthanide coiled coil with nanometre-scale control', Chemical Science. https://doi.org/10.1039/D6SC00813E

Parr, RJ, Santin, YG, Ratkevičiūte, G, Caulton, SG, Radford, P, Gurvič, D, Jenkins, M, Doyle, MT, Mead, L, Silale, A, van den Berg, B, Knowles, TJ, Sockett, RE, Stansfeld, PJ, Laloux, G & Lovering, AL 2025, 'A porin-like protein used by bacterial predators defines a wider lipid-trapping superfamily', Nature Communications, vol. 16, no. 1, 6213. https://doi.org/10.1038/s41467-025-61633-0

Alexander, LT, Follonier, OM, Kryshtafovych, A, Abesamis, K, Bibi‐Triki, S, Box, HG, Breyton, C, Bringel, F, Carrique, L, d'Acapito, A, Dong, G, DuBois, R, Fass, D, Fiesco, JM, Fox, DR, Grimes, JM, Grinter, R, Jenkins, M, Kamyshinsky, R, Keown, JR, Lackner, G, Lammers, M, Liu, S, Lovering, AL, Malinauskas, T, Masquida, B, Palm, GJ, Siebold, C, Su, T, Zhang, P, Zhou, ZH, Fidelis, K, Topf, M, Moult, J & Schwede, T 2025, 'Protein Target Highlights in CASP16: Insights From the Structure Providers', Proteins: structure, function, and bioinformatics. https://doi.org/10.1002/prot.70025

Caulton, SG, Lambert, C, Tyson, J, Radford, P, Al-Bayati, A, Greenwood, S, Banks, EJ, Clark, C, Till, R, Pires, E, Sockett, RE & Lovering, A 2024, 'Bdellovibrio bacteriovorus uses chimeric fibre proteins to recognize and invade a broad range of bacterial hosts', Nature Microbiology, vol. 9, no. 1, pp. 214-227. https://doi.org/10.1038/s41564-023-01552-2

Franklin, A, Salgueiro, VC, Layton, AJ, Sullivan, R, Mize, T, Vázquez-Iniesta, L, Benedict, ST, Gurcha, SS, Anso, I, Besra, GS, Banzhaf, M, Lovering, AL, Williams, SJ, Guerin, ME, Scott, NE, Prados-Rosales, R, Lowe, EC & Moynihan, PJ 2024, 'The mycobacterial glycoside hydrolase LamH enables capsular arabinomannan release and stimulates growth', Nature Communications, vol. 15, no. 1, 5740. https://doi.org/10.1038/s41467-024-50051-3

Al-Jourani, O, Benedict, ST, Ross, J, Layton, AJ, van der Peet, P, Marando, VM, Bailey, NP, Heunis, T, Manion, J, Mensitieri, F, Franklin, A, Abellon-Ruiz, J, Oram, SL, Parsons, L, Cartmell, A, Wright, GSA, Baslé, A, Trost, M, Henrissat, B, Munoz-Munoz, J, Hirt, RP, Kiessling, LL, Lovering, AL, Williams, SJ, Lowe, EC & Moynihan, PJ 2023, 'Identification of d-arabinan-degrading enzymes in mycobacteria', Nature Communications, vol. 14, no. 1, 2233. https://doi.org/10.1038/s41467-023-37839-5

Caulton, SG & Lovering, AL 2023, 'Moving toward a better understanding of the model bacterial predator Bdellovibrio bacteriovorus', Microbiology, vol. 169, no. 8, 001380. https://doi.org/10.1099/mic.0.001380

Alexander, LT, Durairaj, J, Kryshtafovych, A, Abriata, LA, Bayo, Y, Bhabha, G, Breyton, C, Caulton, SG, Chen, J, Degroux, S, Ekiert, DC, Erlandsen, BS, Freddolino, PL, Gilzer, D, Greening, C, Grimes, JM, Grinter, R, Gurusaran, M, Hartmann, MD, Hitchman, CJ, Keown, JR, Kropp, A, Kursula, P, Lovering, AL, Lemaitre, B, Lia, A, Liu, S, Logotheti, M, Lu, S, Markússon, S, Miller, MD, Minasov, G, Niemann, HH, Opazo, F, Phillips, GN, Davies, OR, Rommelaere, S, Rosas‐Lemus, M, Roversi, P, Satchell, K, Smith, N, Wilson, MA, Wu, KL, Xia, X, Xiao, H, Zhang, W, Zhou, ZH, Fidelis, K, Topf, M, Moult, J & Schwede, T 2023, 'Protein target highlights in CASP15: Analysis of models by structure providers', Proteins: structure, function, and bioinformatics. https://doi.org/10.1002/prot.26545

Banks, EJ, Valdivia-Delgado, M, Biboy, J, Wilson, A, Cadby, IT, Vollmer, W, Lambert, C, Lovering, AL & Sockett, RE 2022, 'Asymmetric peptidoglycan editing generates cell curvature in Bdellovibrio predatory bacteria', Nature Communications, vol. 13, no. 1, 1509. https://doi.org/10.1038/s41467-022-29007-y

Harding, C, Cadby, I, Moynihan, P & Lovering, A 2021, 'A rotary mechanism for allostery in bacterial hybrid malic enzymes', Nature Communications, vol. 12, no. 1, 1228. https://doi.org/10.1038/s41467-021-21528-2

Meek, RW, Cadby, IT & Lovering, AL 2021, 'Bdellovibrio bacteriovorus phosphoglucose isomerase structures reveal novel rigidity in the active site of a selected subset of enzymes upon substrate binding', Open Biology, vol. 11, no. 8, 210098. https://doi.org/10.1098/rsob.210098

Lovering, AL & Sockett, RE 2021, 'Microbe Profile: Bdellovibrio bacteriovorus: a specialized bacterial predator of bacteria', Microbiology, vol. 167, no. 4, 001043. https://doi.org/10.1099/mic.0.001043

Harding, CJ, Huwiler, SG, Somers, H, Lambert, C, Ray, LJ, Till, R, Taylor, G, Moynihan, PJ, Sockett, RE & Lovering, AL 2020, 'A lysozyme with altered substrate specificity facilitates prey cell exit by the periplasmic predator Bdellovibrio bacteriovorus', Nature Communications, vol. 11, no. 1, 4817 . https://doi.org/10.1038/s41467-020-18139-8

Comment/debate

Franklin, A, Salgueiro, VC, Layton, AJ, Sullivan, R, Mize, T, Vázquez-Iniesta, L, Benedict, ST, Gurcha, SS, Anso, I, Besra, GS, Banzhaf, M, Lovering, AL, Williams, SJ, Guerin, ME, Scott, NE, Prados-Rosales, R, Lowe, EC & Moynihan, PJ 2024, 'Author Correction: The mycobacterial glycoside hydrolase LamH enables capsular arabinomannan release and stimulates growth', Nature Communications, vol. 15, no. 1, 7155. https://doi.org/10.1038/s41467-024-51724-9

Caulton, SG & Lovering, AL 2024, 'Fly-fishing for flagella: Molecular grappling hooks are the tools of a sticky bacterial predator', Science, vol. 386, no. 6719, pp. 273-274. https://doi.org/10.1126/science.ads6761

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