PhD student profiles

     
     
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Eleanor McMahon
Wellcome Trust 4-year Interdisciplinary PhD Programme, beginning in Autumn 2012

Project title
Structure-function Analyses of Chlamydia Effector Proteins

Principle investigator: Dr Richard Hayward, ISMB, Birkbeck and UCL
Co-investigator: Professor Helen Saibil, ISMB, Birkbeck

 
Background
I first became interested in proteins involved in human infection in 2010 during my 6-week summer Society for General Microbiology studentship in Dr Richard Hayward’s lab. It was here where I first learnt the basic skills required to work in a cell biology lab including mammalian cell culture and fluorescence microscopy. During my third year undergraduate project, I joined Dr Renos Savva’s lab investigating accessory proteins in HIV-1. I graduated in 2012 with a degree in Biochemistry from UCL.
 
Rotations

Rotation 1
I undertook my Chemical Biology rotation in Dr Sanjib Bhakta’s lab studying novel targets for the treatment of Mycobacterium tuberculosis, the bacterium that causes tuberculosis. This involved using surrogate Mycobacterium models to screen anti-tubercular compounds using the solid-based spot culture growth inhibition (SPOTi) assay (Gupta and Bhakta, 2012).

Rotation 2
My Computational Biology project was in structural bioinformatics. I worked in Dr Mark Williams’ lab carrying out a systematic comparison of the structures helical repeat domains, that are commonly involved in protein-protein recognition in eukaryotes, with a view to better understanding their evolutionary and functional relationships.

Rotation 3
My Structural Biology rotation project was undertaken in Dr Richard Hayward’s lab. I decided to complete my PhD in this lab (see below).

 
PhD Project

Chlamydia trachomatis infection poses a significant threat to human health causing infection in an estimated 100 million people worldwide. It is responsible for both sexually transmitted genital tract infections and an ocular infection called trachoma. Chronic infection can lead to infertility and blindness respectively. C. trachomatis is an obligate intracellular pathogen, and occupies a specialised vacuole, called the inclusion, following entry into host cells.

Chlamydia express various effector proteins throughout their developmental cycle within the inclusion. Some of these proteins are secreted via the chlamydial type III secretion system, and subsequently localise to the host cytosol, nucleus or the inclusion membrane. These effectors interact with host proteins to enable bacterial survival, through mechanisms such as binding to key cell signaling proteins or by intercepting metabolite transfer proteins, such as CERT.

My project requires a multidisciplinary approach involving molecular biology, protein expression, biophysical techniques, and confocal and electron microscopy to investigate the structure and function of chlamydial effector proteins both in vitro and in a cellular environment.

 
PhD Project
Guzman J D, Pesnot T, Barrera D A, Davies H M, McMahon E, Evangelopoulos D, Mortazavi P N, Munshi T, Maitra A, Lamming E D, Angell R, Gershater M C, Redmond J M, Needham D, Ward J M, Cuca L E, Hailes H C and Bhakta S ‘Tetrahydroisoquinolines affect the whole-cell phenotype of Mycobacterium tuberculosis by inhibiting the ATP-dependent MurE ligase’ (2015) Journal of Antimicrobial Chemotherapy, published online February 4 2015 ahead of print

 

 

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