Ageing is arguably the major biomedical challenge of the 21st century. In model organisms, the process of ageing can be manipulated by both genetic manipulations and dietary interventions. Although many genes have already been associated with longevity in model systems, which are the most promising for targeting ageing remain unknown and identifying new powerful targets for preserving health in old age would have widespread applications. Likewise, although a few compounds with possible pro-longevity effects are undergoing clinical trials, discovering new compounds that protect against ageing and promote longevity and health in old age is of great importance.
In this project, we aim to identify new genes and compounds with pro-longevity, health-promoting effects. To achieve this, we have already performed sophisticated bioinformatics analyses for prioritizing candidates and demonstrated in model organisms that our predictions yield biologically-relevant results. Therefore, our prioritized candidates for pro-longevity effects will allow us to focus on a relatively small number of high-confidence targets and compounds. These will be studied in well-established worm models for effects on longevity. Besides, healthspan assays will be conducted to determine whether promising drugs improve health in addition to lifespan. Mechanisms of action will also be explored by testing longevity effects in known ageing-related mutants and by employing standard biochemical and molecular techniques. Furthermore, studies in mammalian cells will be performed to assay for potential effects relevant to humans. Specifically, models of induced senescence will be employed to assay for protective roles of genes and drugs. The exact direction of this project and methods to be used, however, will be adapted to fit the research interests and background of the student.
Pro-longevity drugs are already being clinically explored with ongoing clinical trials for several age-related diseases like cancer and type 2 diabetes. This project will provide new pro-longevity genes and compounds which will open translational opportunities to develop human therapies targeting age-related conditions.
Further details about our work on aging and age-related diseases are available at: https://www.liverpool.ac.uk/ageing-and-chronic-disease/staff/joao-de-magalhaes/
The Institute of Ageing and Chronic Disease is fully committed to promoting gender equality in all activities. In recruitment we emphasize the supportive nature of the working environment and the flexible family support that the University provides. The Institute holds a silver Athena SWAN award in recognition of on-going commitment to ensuring that the Athena SWAN principles are embedded in its activities and strategic initiatives.
Training: This project will provide a rich and diverse training in contemporary methods in genetics of model organisms, pharmacology, biochemistry and cell and molecular biology techniques applied to ageing research and dietary manipulations of ageing in particular.
In addition to the generic skills training that is provided through the Institute and University PhD programme, the student will be supported by an excellent infrastructure and will work closely with experts on the biology and genetics of ageing, model organisms, pharmacology, nutrition, and cell and molecular biology. This diverse and stimulating environment will allow a creative and talented student to develop key skills and the project is flexible enough to allow the student to develop his or her own research interests. The student will be well-prepared for a successful career in research and in biotechnology.
Potential applicants are encouraged to contact Dr de Magalhaes ([email protected]
) in the first instance for an informal discussion.
To apply please send your CV and a covering letter to Dr de Magalhaes ([email protected]
with a copy to [email protected]
There is no funding attached to this project. Details of costs can be found on the University website. The successful applicant will be expected to provide the funding for tuition fees and living expenses as well as research costs of £1,000 to £6,000 per annum, depending on the type of project.
Calvert S, Tacutu R, Teixeira R, Ghosh P, de Magalhães JP (2016) “A network pharmacology approach reveals new candidate caloric restriction mimetics in C. elegans.” Aging Cell 15:256-266.
Wood SH, van Dam S, Craig T, Tacutu R, O’Toole A, Merry BJ, de Magalhães JP (2015) “Transcriptome analysis in calorie-restricted rats implicates epigenetic and post-translational mechanisms in neuroprotection and ageing.” Genome Biology 16:285.
de Magalhaes et al. (2012) "Genome-environment interactions that modulate aging: powerful targets for drug discovery." Pharmacological Reviews 64:88-101.