Dr Helen O'Hare

Lecturer

Lab: 136 
Office (MSB): 129a

Telephone: +44 (0)116 252 2947

Email: hmo7@le.ac.uk

Research

The main aim of my research group is to determine the molecular mechanisms by which bacteria sense and respond to their environment, with a particular focus on protein kinase G in the human pathogen Mycobacterium tuberculosis.

Phosphorylation at serine and threonine emerged as a ubiquitous mechanism of signal transduction in bacteria from genome sequencing in the 1990s. Serine and threonine protein kinases are now known to regulate critical bacterial processes including central carbon metabolism and cell division, but identification of the stimuli of kinase activation and the downstream effects of kinase activation are outstanding questions in the field.

My group study the complete PknG signalling pathway, from activation by amino acids to the downstream roles of kinase substrates in regulating central metabolism, with the result that PknG is one of only a handful of bacterial S/T kinases for which the activation stimuli are known, and arguably the only bacterial FHA-mediated signalling pathway with a complete molecular description (FHA=forkhead associated domain, a ubiquitous phospho-threonine recognition domain).

We are also working on the conserved pathways 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 Departments of Respiratory Science and Molecular and Cell Biology to validate anti-TB drug targets and for structure based drug discovery (Russell Wallis), to study protein phosphorylation at the level of the phosphoproteome and in regulation of bacterial cell growth (Galina Mukamolova), and to study the function of these signalling pathways in infection models (Leicester TB Research Group).

Publications

Selected publications

Iswahyudi, Mukamolova GV, Straatman-Iwanowska AA, Allcock N, Ajuh P. Turapov O, O’Hare HM (2019). Mycobacterial phosphatase PstP regulates global serine threonine phosphorylation and cell division Scientific Reports 9(1):8337

Wagner T, Andr.-Leroux G, Hindie V, Barilone N, Lisa MN, Hoos S, Raynal B, Vulliez-Le Normand B, O’Hare HM, Bellinzoni M, Alzari PM (2019). Structural insights into the functional versatility of an FHA domain protein in mycobacterial signaling Science Signaling 12(580).

Bhattacharyya N, Nkumama IN, Newland-Smith Z, Lin LY, Yin W, Cullen RE, Griffiths JS, Jarvis AR, Price MJ, Chong PY, Wallis R, O’Hare HM (2018). An aspartate-specific solute-binding protein regulates protein kinase G activity to control glutamate metabolism in Mycobacteria. mBio 9(4): mBio00931-18.

Barbara Rieck, Giulia Degiacomi, Michael Zimmermann, Alessandro Cascioferro, Francesca Boldrin, Natalie R. Lazar-Adler, Andrew R. Bottrill, Fabien le Chevalier, Wafa Frigui, Marco Bellinzoni, Mar´ıa-Natalia Lisa, Pedro M. Alzari, Liem Nguyen, Roland Brosch, Uwe Sauer, Riccardo Manganelli, Helen PknG senses amino acid availability to control metabolism and virulence of Mycobacterium tuberculosis. Barbara Rieck, Giulia Degiacomi, Michael Zimmermann, Alessandro Cascioferro, Francesca Boldrin, Natalie R. Lazar-Adler, Andrew R. Bottrill, Fabien le Chevalier, Wafa Frigui, Marco Bellinzoni, Mar´ıa-Natalia Lisa, Pedro M. Alzari, Liem Nguyen, Roland Brosch, Uwe Sauer, Riccardo Manganelli, Helen M. O’Hare. PknG senses amino acid availability to control metabolism and virulence of Mycobacterium tuberculosis.  PLoS Pathogens. 2017

Garton NJ, O'Hare HM. Tuberculosis: feeding the enemy. Chem Biol. 2013;20(8):971-2.

Ventura M, Rieck B, Boldrin F, Degiacomi G, Bellinzoni M, Barilone N, Alzaidi F, Alzari PM, Manganelli R, O'Hare HM. GarA is an essential regulator of metabolism in Mycobacterium tuberculosis. Mol Microbiol. 2013;90(2):356-66.

Bortoluzzi A, Muskett FW, Waters LC, Addis PW, Rieck B, Munder T, Schleier S, Forti F, Ghisotti D, Carr MD, O’Hare HM. Mycobacterium tuberculosis RNApolymerase binding protein A (RbpA) and its interactions with sigma factors. J Biol Chem. 2013 May 17;288(20):14438-50

Wagner T, Bellinzoni M, Wehenkel A, O'Hare HM, Alzari PM. Functional plasticity and allosteric regulation of alpha-ketoglutarate decarboxylase in central mycobacterial metabolism. Chem Biol 2011;18(8):1011-20

Nott TJ, Kelly G, Stach L, Li J, Westcott S, Patel D, Hunt DM, Howell S, Buxton RS, O'Hare HM, Smerdon SJ. An intramolecular switch regulates phosphoindependent FHA domain interactions in Mycobacterium tuberculosis. Sci Signal 2009;2:ra12.

Full list of publications

Teaching

I am the director of the BSc in Medical Microbiology and BSc in Biological Sciences (microbiology)

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Contact Details

Department of Respiratory Sciences
Maurice Shock Medical Sciences Building
University Road
Leicester LE1 9HN

Head of Department: Professor Mike Barer

PA: Alison Brown

General enquiries

T:+44 (0)116 252 2951