Simple interventions, such as diet, single-gene mutations and drugs, can increase lifespan of the tiny nematode worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster. Lowered food intake, known as dietary restriction, and genetically or pharmacologically reduced activity of the nutrient-sensing insulin/insulin-like growth factor/TOR (IIT) signaling network have proved to increase healthspan in worms, flies and mice. There is thus robust evolutionary conservation of mechanisms of ageing1,2. These interventions produce substantial improvements in health and function during ageing and delay the onset of a wide range of ageing-related diseases, opening up the prospect of a broad-spectrum, preventative medicine for the diseases of ageing.
The mechanisms by which these interventions improve health during ageing are not understood. Key transcription factors are required for extension of lifespan by reduced nutrient intake and lowered activity of the IIT network. Investigation of how gene expression is altered so as to improve health during ageing is a powerful approach to identifying candidate effector genes and mechanisms. An important step in this process will be to integrate observed gene expression changes in different tissues, and to identify conserved mechanisms in different organisms.
This project is to do the primary analysis of RNA-seq and large scale DNA-protein interaction data3 generated in worms (Schuster lab) and flies (Partridge lab). In addition, the student will build an interaction/regulatory network from publically available data (e.g. modENCODE data4) that can be analysed to reveal novel genes and processes involved in the regulation of lifespan. Initial work will concentrate on intestine-specific gene expression changes in worms and flies in response to the activation of a forkhead transcription factor and the identification of processes that are regulated in both species. Identification of conserved mechanisms that regulate lifespan is a key goal of this work and the Institute of Healthy Ageing (IHA) and presents an exciting opportunity to identify candidate genes and processes that can be tested in other species and eventually translated into an understanding of human health and ageing.
Applicants should have Master’s degree or equivalent in a relevant field. For example, a strong mathematical or computational background and deep interest in biology of ageing or a biology background with previous experience in programming and bioinformatics.
Please e-mail cover letter and a full CV to Dr. Eugene Schuster (firstname.lastname@example.org
) before 25th Nov. 2012. The cover letter must outline your interest in the project and contain a clear statement of your eligibility for a studentship (only available to EU citizens). CV must include contact details for two academic referees and course marks for undergraduate and/or masters degrees.
The post is only open to UK/EU citizens. Applicants should have Master’s degree or equivalent in a relevant field. For example, a strong mathematical or computational background and deep interest in biology of ageing or a biology background with previous experience in programming and bioinformatics.
Good oral, written, and presentation skills.
Well-organised, attention to detail, and ability to meet deadlines.
Ability to think logically, create solutions, and make informed decisions.
Essential: Fluency and clarity in spoken English, good written English, ability to work collaboratively as part of team, commitment to high quality research
1. Fontana, L. et al. Extending healthy life span--from yeast to humans. Science 328, 321-6 (2010).
2. Kenyon, C.J. The genetics of ageing. Nature 464, 504-12 (2010).
3. Schuster, E. et al. DamID in C. elegans reveals longevity-associated targets of DAF-16/FoxO. Molecular systems biology 6, 399 (2010).
4. Contrino, S. et al. modMine: flexible access to modENCODE data. Nucleic acids research 40, D1082-8 (2012).