Life after MOACAfter completing my PhD I moved to Cambridge, the home of human genetics/genomics in the UK, to begin working at the Wellcome Trust Sanger Institute. I have been working for the past 2 years in the Human Genetics Team under Matthew Hurles, looking into the role of genomic variation in the population on complex diseases. My current role is as a statistical geneticist, where the computational biology and statistical aspects of the MOAC doctoral training course have proved invaluable. In particular, I am responsible for the processing and analysis of an extremely large genome-wide association study at one of the largest genome research institutes in the world.
Copy number variants (CNVs) are segments of DNA > 1kb in size that are found to have variable copy numbers in the population. The simplest of these are deletions (where the DNA is missing from one or both alleles when compared to the reference) and duplications (where the DNA is found to be duplicated on one or both alleles when compared to the reference). However, the mechanisms underlying such mutations often result in much more complex CNVs. Working with the Wellcome Trust Case Control Consortium, we genotyped > 19,000 European individuals (~2,000 case individuals from 8 disease cohorts and ~3,000 controls) at known CNV loci using a bespoke CNV genotyping array to identify CNVs that are associated with any of the 8 diseases. This work has now been completed and the resulting publication has been accepted by Nature and should be in print early 2010.
I am now set to begin a new postdoctoral position working on the role of histone modifications in cancer, working under Tony Kouzarides at the Gurdon Institute in Cambridge. This role will involve the analysis of a large number of chromatin immunopreciptation sequencing (ChIP-Seq) experiments, and the design and implementation of tools for inferring biological meaning from these data
After completing a Bachelors degree in Mathematics at the University of Warwick in 2003, attaining a class 2:1 degree with Honours, I decided to continue my training at the University and undertook the MOAC Doctoral Training course that same year. I completed my MSc in 2004, attaining a first class degree with distinction. I have now begun a three year PhD course (see below for details), aiming to complete this for 2007.
My current skills focus mainly on bioinformatic techniques, particularly those involved with the use of microarrays and the subsequent analysis of high-throughput data.
My wet lab experience includes laser capture microdissection, small-sample RNA preparations, microarrays, immunohistochemical staining, PCR and quantitative RT PCR.
My theoretical experience includes extensive use of the gene expression analysis software suite Genespring GX (including close collaborative work with Ewan Hunter of Agilent Technologies on implementing additional analysis techniques within Genespring GX Version 8) and extensive use of the open-source statistical programming language R (particularly Bioconductor , a collection of packages for R written for use in the field of bioinformatics). I am proficient in programming in R, Matlab and Tcl/Tk, and I have familiarity with C++, Fortran and JAVA.
Outside of my PhD, I am an avid martial artist and hold a black belt (1st Dan) in the Korean art of Tae Kwon Do. I am an active member of the University of Warwick Tae Kwon Do Club, was President of the club for the academic year 2005-2006, and have been a fully qualified instructor with the club since 2006. I also currently hold the position of President for the ITF branch of the British Student Tae Kwon Do Federation, a national forum for University level Tae Kwon Do clubs throughout the United Kingdom.
Title: Life or Cell Death: Deciphering c-Myc Regulated Gene Networks in Two Distinct Tissues
Supervisors: Mike Khan (Biological Sciences) and David Epstein (Mathematics)
Collaborators: Stella Pelengaris (Medical School), Helen Bird (Biology Services), Heather Turner (Statistics) and Ewan Hunter (Agilent Technologies)
Advisory Committee: Robert Old (Biological Sciences), Manu Vatish (Medical School), James Lynn (Warwick HRI )
My Phd project focuses on the proto-oncogene c-Myc, a gene which is known to be deregulated in the majority of human cancers. The protein product is a transcription factor involved in a large range of biological processes, such as cell-cycle regulation, cell growth, loss of differentiation, loss of cell-cell contact and induction of angiogenesis. The c-Myc protein has also been found to be heavily involved in apoptosis, acting as its own tumour suppressor when biological functions go askew.
c-Myc has been found to regulate the expression of a very large number of genes, although it is not yet clear as to whether this is due to direct c-Myc interaction, or whether these changes occur as a downstream result of c-Myc. An in vivo model has been created that allows us to activate and deactivate a transgenic form of the c-Myc onco-protein, allowing direct control over the time scale of c-Myc induced changes.
It has been shown that activation of c-Myc in supra-basal epidermal skin cells results in entry of the cells into the cell cycle (G1-S phase), loss of differentiation, an increase in cell proliferation, and the onset of tumour-like growths (papilloma). However, activation of c-Myc in the β-cells of the pancreatic islets of langerhans (sole producers of insulin within the body) results predominantly in a massive apoptotic response, reduction in islet mass, and eventual death.
My project aims to use microarray analysis to analyse the reasons behind the dichotomy of c-Myc functionality shown between these two tissues, and to find putative c-Myc target genes involved. A novel technique for multi-variable analysis of microarray data using linear models will be developed to allow significance analysis on this complex data set.
MSc Mini Projects
As part of the interdisciplinary nature of the course, the MSc program required the completion of three mini projects, each lasting 8 weeks and taking place in one of the three disciplines of Chemistry, Biological Sciences and Mathematics/Computing.