FULLY FUNDED PHD - Disrupting Age-Related Disease: Discovery and development of novel senolytics

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The molecular mechainsms driving cellular senescence, where-by cells simultaneously withdraw permanently from the cell cycle and escape apoptosis, remain elusive.

A strikingly important feature of senescence cells (SC) is their low-level senescence-associated secretory phenotype (SASP), characterised by a wide variety of cytokines, chemokines, growth factors and proteases.

This SASP is identified to accumulate with age, creating a deleterious low-level chronic inflammatory microenvironment. This mechanism is hypothesised to accelerate/promote ageing and age-related diseases, including cancer.

Unsurprisingly, discovery and development of therapies that can target the destruction of SCs is a highly attractive and vibrant area of R&D.

Project Aims:
(i) Identify novel/validated protein-protein interactions (PPIs) found to drive ageing/age-related disease.
(ii) Discover and develop highly selective cell-penetrating peptide disrupters (CPP-D) of said PPIs.
(iii) Develop biochemistry/pharmacology of CPP-Ds.
(iv) Demonstrate disruption of PPI using developed CPP-Ds.
(v) Establish appropriate senescence associated cellular models/assays.
(vi) Validate senolytic capabilities of developed CPP-Ds in vitro
(vii) Identify LEAD senolytic compound(s) for appropriate pre-clinical assessment.

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