Catriona Smith
UNDER CONSTRUCTION - LABCOATS MUST BE WORN AT ALL TIMES! (hard hats optional)
Background
Research Interests
In reading for my undergraduate degree, I have developed a keen interest in the molecular biology of cells and systems under duress in infection and disease states, with particular awareness of the potential for application of the various '-omics' fields.
- Proteomics
- Network and pathway analysis
- Modelling
- Pathogenesis
- Drug target identification
Education
2011-present: PhD: University of Warwick, UK
Title: Targeting the human eIF4E dorsal site using peptide-mimetics.
Supervisor: Prof. John McCarthy
2010-2011: MSc Systems Biology: University of Warwick, UK
Modules: Cellular Systems and Biomolecules, Biological Systems, Technologies for the Study of Systems Biology, Microscopy and Imaging, Statistics for Data Analysis, Mathematical Models of Biological Systems, Numerical Methods for Modelling, Quantitative Biology.
Bench rotation project: Targeting the human eIF4E dorsal site using peptide-mimetics.
Dry rotation project: Towards modelling tunable intracellular signalling cascades.
2007-2010 : BSc (Hons) Microbiology : University of Leeds, UK
Key modules: Applied and Environmental Microbiology, Advanced Topics in Microbiology, Medical Microbiology, Viruses and Virus-Host Interactions, Eukaryotic Genes: Cloning and Expression, Function/Diversity in Microorganisms, Biochemistry: Cells and Organisms, Prokaryotic Genetics.
Dissertation: A bioinformatic analysis of the avian nucleolar proteome in mock- and virus-infected cells.
Experience
2011 - MSc rotation project 2 (University of Warwick)
"Targeting the human eIF4E dorsal site using peptide-mimetics"
ABSTRACT - A critical step in cap-dependent translation initiation in eukaryotes involves the association of eIF4G with the cap-binding protein eIF4E, to form eIF4F, recruiting the ribosomal 43S complex to the 5' end of the mRNA. The eIF4F interaction can be blocked by small (~12kDa) heat-stable regulatory proteins called 4E-binding proteins (4E-BPs), via competition with eIF4G for the same eIF4E dorsal site. 4E-BPs and eIF4G share the same Y(X)4Lθ motif (Tyr; X=variable; Leu; θ=hydrophobic) binding domain. The 4E-BPs are intrinsically unstructured proteins and biophysical studies have suggested that there is little or no structure in 4E-BP1 in solution but that the binding region becomes more structured (~50% helical) upon complexing with eIF4E. A 17mer peptide corresponding to 4E-BP1 residues 49-68, sufficient for inhibition of eIF4E, has been shown to have a similar affinity for eIF4E to that of full-length 4E-BP1.
Recent work in the McCarthy lab has identified the role of highly conserved solvent-facing residues not directly involved in specific 4E-BP1:eIF4E interactions as influencing the natively unfolded motif to fold into binding conformation. We are characterising the maximally stabilized α-helical conformation to test the predictions of this model and to determine the ability of 4E-BP1-derived peptides to act as inhibitors of translation.
2011 - MSc rotation project 1 (University of Warwick)
"Towards modelling tunable intracellular signalling cascades"
ABSTRACT - It is known that the mitogen-activated protein kinase (MAPK) cascade provides biological systems with an ultra-sensitive switching mechanism for sensing and responding to changes in environmental stimuli. In addition to transducing extracellular signals from membrane to nucleus, this is also thought to function in both amplification of signal and damping of noise. The results obtained in this study provide us with some insight into the aspects of the cascade that contribute to each of these activities. As well as providing understanding of the function of each part of the cascade, the simulations demonstrate that the natural system is optimised for signal amplification and noise attenuation, giving an evolutionary perspective on how and why the MAPK developed as a dual-phosphorylated, multiple kinase system. Using this understanding of the system, we propose that with the growing fields of synthetic biology and protein engineering, it will be possible to design pre-tuned MAPK cascades for use in synthetic cells and circuits.
2010 - Summer Internship (Woods Hole Marine Biological Laboratory)
I worked under Holly Miller, director of the Scientific Informatics Group at the Marine Biological Laboratory (Woods Hole, MA), beta-testing a forthcoming website to improve functionality and usability.
Guest post on the group's Biology of Aging Blog.
2009/10 - Undergraduate Dissertation Project (University of Leeds)
"A bioinformatic analysis of the avian nucleolar proteome in mock and infected cells"
ABSTRACT - The nucleolus is a subnuclear structure whose primary role was until recently thought to be ribosome biogenesis, regulation of cell cycle and response to cell stress. Due in a large part to mass spectroscopy-based approaches to the elucidation of the nucleolar proteome, it has come to light that the nucleolus plays a role outside its traditional function in ribosome biogenesis. The nucleolus is also targeted by proteins associated with cancer and pathogens, with many viral proteins known to localise to this structure. It has been observed that the nucleolus can change morphology in virus-infected cells. This may correspond with a change in proteome.
This work was undertaken to elucidate the avian nucleolar proteome as a functional dataset and to explore how the nucleolus responds to infection with avian infectious bronchitis virus. The study presents the first solution to the avian nucleolar proteome and begins to explore the network pathways involved during infection with avian infectious bronchitis virus.
2010 Access here
2009 - Summer Studentship (University of Leeds)
"Characterisation of novel inhibitors targeting bacterial RNA polymerase"
SUMMARY OF PROJECT AIMS AND OBJECTIVES - The original objectives of this research project were to determine the in vitro antibacterial activity of a panel of reported bacterial RNA polymerase (RNAP) inhibitors against Staphylococcus aureus and to confirm their modes of action (MOA) as inhibitors of RNA synthesis using a whole-cell reporter-based system.
It was decided to expand the programme to better characterise the MOA of these inhibitors by generating S. aureus mutants displaying resistance to the agents, followed by cross-resistance and fitness analyses and identification of RNAP subunit mutations using DNA sequencing.
There was also the opportunity to begin to evaluate and characterise a novel rifampicin analogue, designed and synthesised at the University of Leeds.
Mariner, K et al., 2011 Access here
British Society for Antimicrobial Chemotherapy (BSAC) Summer Scholarship Funding awarded.
Conferences
2013
- EMBL PhD Symposium: Competition in Biology - The race for survival from molecules to systems
EMBL Heidelberg, DE
Abstact submitted for oral presentation
- Translation UK Post-transcriptional control: mRNA translation, turnover and localisation
University of Kent
Poster presented, Conference bursary awarded
- Systems Biology DTC: Annual conference
Stratford
Poster presented - First prize awarded
2012
- International Workshop on Systems and Synthetic Biology
Hotel Bon Sol, Illetes, Mallorca
Oral presentation, Conference bursary awarded
- Translation UK Post-transcriptional control: mRNA translation, turnover and localisation
University of Southampton, UK
Oral presentation
2011
- Translation UK Post-transcriptional control: mRNA translation, turnover and localisation
Cambridge University, UK
Poster presented
- EMBO Conference Series: Protein Synthesis and Translational Control
EMBL Heidelberg, DE
Poster presented
2009
- British Science Festival
Surrey, UK
(Student Bursary awarded as essay competition prize)
Publications
Mariner, K; McPhillie, M; Trowbridge, R; Smith, C; O'Neill, AJ; Fishwick, CWG; Chopra, I Activity of and development of resistance to corrallopyronin-A, a bacterial RNA polymerase inhibitor Antimicrobial Agents and Chemotherapy, 55, 2516-2416, 2011 Access here
Elucidation of the avian nucleolar proteome by quantitative proteomics using SILAC and changes in cells infected with the coronavirus infectious bronchitis virus. Proteomics, 10, 3558-3562, 2010 Access here
Catriona Smith
c dot s dot l dot smith at warwick dot ac dot uk
Systems Biology Doctoral Training Centre
Senate House
University of Warwick
Gibbet Hill Road
Coventry
CV4 7AL
