Intra-genomic Conflict and Medical Disorders
Dr Francisco Ubeda and Prof. Vincent A.A. Jansen
Intra-genomic conflict defies the logic of natural selection: why would natural selection favor any gene whose expression reduces the fitness of its host? However intra-genomic conflict has left its signature in many molecular mechanisms. A paradigmatic example of evolution driven by intra-genomic conflict is the case of genomic imprinting where conflict between paternally inherited and maternally inherited genes in the same individual results in silencing of one gene but not the other (1).
Recently, genomic imprinting (and intra-genomic conflict in general) has been linked to several diseases (2). For example, deletion of the PWS/AS cluster of imprinted genes causes Prader-Willi syndrome (PWS) when the deletion is paternally inherited but Angelman syndrome (AS) when it is maternally inherited (3). The clinical phenotype, regarding appetite and activity levels, of children suffering from these syndromes is the reverse: poor sucking and low weight in children with PWS but insatiable appetite and obesity in children with AS (3).
This intriguing reversal of the clinical phenotype of a deletion is best explained in the light of conflict between genes with different parental origin. In particular, it can be explained when paternally inherited copies favor a greater allocation of maternal resources to offspring than the maternally inherited copy does (4). We are interested in further exploring the role of intra-genomic conflict in disease. Can we predict the risk of developing diseases caused by genes in conflict? Can we suggest epigenetic modifications that may palliate some symptoms?
In this project we will formulate mathematical models for the evolution of intra-genomic conflict and make specific predictions about the outcomes. We will test the predictions of our models against the medical literature. This research will require a trans-disciplinary approach that uses mathematical and computational models to synthesize the fields of molecular biology, genetics, medicine, evolutionary biology, and behavioral ecology. We hope to apply this approach to understand the evolution of genomic imprinting, sex-determination, and disease virulence among others.
This project is suitable for candidates with some background or experience in mathematical modeling or simulation at undergraduate level. We are looking for candidates, either with a background in the life sciences, and experience in mathematical or simulation modeling, or for candidates with a background in a quantitative subject (e.g. mathematics, computer science, physics) and an affinity for research in ecology and evolution.
The studentship will be held in the School of Biological Sciences of Royal Holloway, University of London. The research in the School covers the breadth of biology and hosts a number of theoretical researchers. The School was ranked among the best UK Bioscience Departments in the last research assessment (RAE 2008). The scenic Royal Holloway campus is on the outskirts of London
The studentship has a maintenance allowance of £15726 per annum for 3 years and a UK/EU tuition fee waiver . We expect candidates to have a 2.1 or first class degree (or equivalent if not a UK degree).
Apply before the 4th of March following the link http://www.rhul.ac.uk/biologicalsciences/prospectivestudents/postgraduateresearch/phdstudentships2013v2.aspx ; get in touch with Tracey Jeffries (Tracey.Jeffries@rhul.ac.uk) for any application queries. If you are interested in applying please contact us informally before the deadline at F.Ubeda@rhul.ac.uk or Vincent.firstname.lastname@example.org