I have recently completed my PhD titled 'Mechanisms of GPCR signal regulation in fission yeast' in Dr Graham Ladds group at the University of Warwick Medical school (Web link) in the UK. I am a Science Technology Engineering and Mathematics (STEM) ambassador for Coventry and North Warwickshire and actively involve myself in science communication and outreach events.

Research interests

Cells communicate with each other and respond to environmental cues by sending and receiving signals. Many external signals (ligands) are detected through G protein-coupled receptors (GPCRs), a major class of transmembrane proteins. GPCRs transduce these external signals into appropriate intracellular responses thus enabling the cell to adapt to its environment. Malfunctions in these signalling pathways can lead to a range of human diseases and hence, GPCRs have become attractive candidates for pharmacological design.

Due to the complex nature of signalling networks and the often-large number of diverse signalling molecules involved, it is difficult and time-consuming to interpret the role of each individual molecule in the network. As a result, many researchers are now taking systems biology approaches to study cell signalling. My research utilises a combination of in vivo experimentation with computational modelling, to aid the mechanistic understanding of desensitisation or termination of G protein signalling.

Studying GPCR signalling in higher eukaryotes is complex since the activation of a single receptor has the ability to induce numerous intracellular responses; therefore a more tractable system is desired. The pheromone-response pathway in the fission yeast Schizosaccharomyces pombe (S. pombe) provides a simplified system for studying signalling through GPCRs. I used mathematical modelling to aid the understanding of GPCR signalling in S. pombe and to inform experimental design. Specifically, a novel ordinary differential equation model describing all known downstream signal transduction, regulation and termination events was created.

Although the model accurately predicts the cellular response to GPCR signalling it could only reproduce the biological plateau in temporal data with the addition of a GPCR degradation term (of yet an unknown mechanism). This motivated the investigation of how GPCRs in S. pombe are internalised from the plasma membrane in response to ligand stimulation.

The primary mechanism for signal termination is via internalisation of the GPCR. My work has identified three potential casein kinases (Cki1, Cki2 and Cki3) that promote internalisation of the S. pombe GPCR Mam2. Microscopy analyses in combination with quantitative transcriptional, cell growth and cell cycle position assays uncovered a novel role for these kinases: that Cki2 regulates cell size during vegetative growth, Cki1 and Cki3 regulate the GPCR-response pathway and that Cki3 is essential for completing cytokinesis in S. pombe that have already undergone formation of a conjugation tube in response to ligand. Confocal microscopy of fluorescent labelled Mam2 indicated a role for Cki2 in the internalisation and hence termination of the GPCR-response pathway. These findings add to the growing body of evidence that casein kinases are implicated in GPCR desensitisation.

Publications

Mos M, Esparza-Franco MA, Godfrey EL, Richardson K, Davey J, Ladds G. 'The role of the RACK1 ortholog Cpc2p in modulating pheromone-induced cell cycle arrest in fission yeast'. PLoS One. 2013 Jul 3; 8

Science Communication

Presentations

Biomedical cell biology division seminar - The University of Warwick, UK, Sept 2013

*Systems Biology DTC annual conference - Stratford, UK, June 2013

Systems Biology DTC monthly seminar - The University of Warwick, UK, Feb 2013

Molecular pharmacology of G Protein-Coupled Receptors - Monash University, Australia, Dec 2012

*International Student Conference - Nijmegen University, Netherlands, Nov 2010

Biomedical cell biology division seminar - The University of Warwick, UK, July 2012

Posters

Molecular pharmacology of G Protein-Coupled Receptors - Monash University, Australia, Dec 2012

*Systems Biology DTC annual conference - Yorkshire, UK, June 2012

British Pharmacology Society conference - Leicester University UK, April 2012

*Joint Systems Biology DTC conference with Manchester and Oxford University - The University of Warwick, UK, June 2012

* = award winning talks or presentaions