Dr Helen O Hare

I joined the University of Leicester in 2008 firstly as a Research Fellow and later as an Associate Professor in microbiology. Previously I worked as a research fellow at the Swiss Federal Institute of Technology developing methods to detect protein-protein interaction to understand Mycobacterium tuberculosis drug targets and as a post doctoral researcher at the University of Cambridge using directed evolution approaches to study enzyme specificity in antibiotic biosynthesis.

• Molecular mechanisms of bacterial physiology
• Structural biology: X-ray crystallography and Cryo-EM
• Actinobacteria in disease, industry and the environment, and evolutionary specialisation of human pathogens

The O’Hare group study bacteria at the molecular level, with a particular focus on the human pathogen Mycobacterium tuberculosis and on bacteria used in industry. Recent achievements include the discovery of a protein kinase signalling pathway that allows M. tuberculosis to sense amino acids produced by human cells in order to regulate its own metabolism.

Molecular mechanisms of sensory perception and metabolic regulation in bacteria

Globally, M. tuberculosis is the leading cause of death from a single infectious agent. Molecular-level understanding of how this bacterium senses and responds to changing conditions in the human lung helps understand how these bacteria survive immune defences, and are slow to respond to drug treatment. Protein kinases regulate important bacterial processes including central metabolism and cell division.

We are interested in deciphering fundamental principles of bacterial regulation, by combining molecular microbiology with protein biophysics and structural biology. One area of interest is PknG, a protein kinase that is essential for virulence. We have identified stimuli that activate PknG, and substrates of PknG that regulate the TCA cycle and amino acid metabolism. We are working to understand how this transmembrane sensory complex changes conformation to transmit information across the membrane to activate the kinase.

This signal pathway is conserved in the industrial “workhorse” Corynebacterium glutamicum (used to produce >$6 billion dollars of amino acids per year) and the antibiotic producing Streptomyces (>$1billion dollar market).>

We collaborate with groups within the Institute and the Leicester TB Research Group to validate anti-TB drug targets for structure based drug discovery, to study protein phosphorylation at the level of the phosphoproteome and in regulation of bacterial cell growth, and to study the function of these signalling pathways in infection models.

• Bacterial sensory perception and signalling
• Mycobacterium tuberculosis
• Bacterial metabolism: central metabolism or secondary metabolism including antibiotic biosynthesis
• Structure-function relationships of bacterial proteins

I am the programme director for BSc Medical Microbiology and BSc Biological Sciences (microbiology) and associated MBiol courses.

I teach on modules in years 1-3 of Biological Sciences such as BS1040 The Cell MB2020 Medical Microbiology MB3020 Advanced topics in medical microbiology.