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Dissecting the telomere-independent pathways underlying cellular senescence. (360G-Wellcome-078305_Z_05_Z)

Cellular senescence is an irreversible program of cell cycle arrest that is triggered in normal somatic cells in response to a variety of intrinsic and extrinsic stimuli including alteration in telomere length and structure, DNA damage, physiological stress and activation of certain oncogenes. It can compromise tissue repair and regeneration and contribute to tissue and organismal ageing due to depletion of stem/progenitor cell compartments. It can also lead to removal of defective and potentially cancerous cells from the proliferating pool thereby preventing tumour development. The underlying mechanism that controls cellular senescence and the signal transduction pathways involved are not fully understood. We have developed a novel human mammary fibroblast cell system for dissecting the telomere-independent pathways that underlie this process and initiated a systematic analysis to identify the associated changes in the transcriptome. Our aim is to functionally validate genes that we have already identified, extend the transcriptional profiling to encompass all human genes and to carry out a genome wide gain of function RNA interference screen. Collectively, implementation of these strategies will enable us to dissect the telomere independent activities and pathways critical for regulating the finite proliferative potential of normal human cells.


17 Oct 2005

Grant details
Amount Awarded 250123
Applicant Surname Jat
Approval Committee Molecules, Genes and Cells Funding Committee
Award Date 2005-10-17T00:00:00+00:00
Financial Year 2005/06
Grant Programme: Title Project Grant
Internal ID 078305/Z/05/Z
Lead Applicant Prof Parmjit Jat
Planned Dates: End Date 2009-12-31T00:00:00+00:00
Planned Dates: Start Date 2006-01-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London
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