Prof.

Robert Lightowlers Director, ICaMB and Professor of Molecular Neuroscience, Wellcome Trust Centre for Mitochondrial Research, Health, Institute for Ageing and

Newcastle University, Newcastle upon Tyne NE2 4HH Date: 10 September, 2012

Ref: IA054

Dear Prof. Robert Lightowlers,

I am writing to apply for the integrated PhD position on Investigating the role of mitochondria in health and disease available at the Institute for Ageing and Heath as advertised in the Newcastle University website. This is an area of research which is both relevant to my interests and academic career and I would be quite interested in pursuing it a 3 year doctorate.

I have completed my MSc in Bioinformatics and Computational Systems Biology from Newcastle University and now seek a PhD in a related field of Biology. While my undergraduate training in Information Technology does not exactly fit this PhD's requirements, I believe my Masters and further work experience in bioinformatics gives me a kind of biological background and technical expertise you would ideally be looking for in a candidate. Additionally, my work experience during several projects in MSc and even after has prepared me for a work in biology research. During the course of my Masters I undertook several research projects as an individual and as a team as well. My MSc dissertation was related to detecting novel SNPs and indels in GS FLX sequenced BRCA 1 and BRCA 2 gene amplicons. Currently, I am working as a visiting researcher for the bioinformatics group at the School of Computing Science, Newcastle University on a project related to clinical diagnostics. My research deals with identifying virulence and toxin producing genes in sequenced metagenomic samples collected from hospital environment. The developments in my research work are to form part of a publication currently under progress by my supervisors. While my projects and experiences aren't exactly related to the proposed doctorate, I believe that with it I have the right motivation and skills of being entirely capable to take up serious research work in a field related to clinical research, genetics and medical sciences.

I have always harboured an interest towards biological and health sciences and would like to contribute to it, particularly in the area which has tremendous potential to change lives. It is evident from past research works that not all diseases are inherited by germline mutations. Mutations of different kinds in cell organelles particularly mitochondria can have even greater impact on the on-set of age dependant chronic

diseases. Examples of such diseases are mostly associated with neurological or muscular disorders. Variations in the mitochondrial genes can have great impact the synthesis of proteins required for ATP synthesis. Studies have shown that even similar kind of somatic mitochondrial DNA mutations can express inconsistently in different people. Such inconsistency have been explained by the relative percentage of affected tissues. It is important to find out what other diseases could be a possible expression of such case. A combination of Next Generation Sequencing technologies and comparative analysis of mitochondrial genes and its translated proteins is one of the approaches that could help us identify pathogenic gene mutations and its associated clinical complications. I have gathered from one of your papers that association of nuclear gene defects in mitochondrial translations could also lead to severe under-diagnosed lethality. It is therefore, suggested to understand the systems biology of such interactions to review fatality of such mutations.

I would greatly appreciate if we could meet for an interview as soon as possible. I have attached my CV and referee details (two) for your reference. Lastly, I would like to thank you for your time and for considering my application. I look forward to hearing form you.

Yours Sincerely, Prisni Rath