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We are pleased to announce that our biomaterials/ biomechanics/cell engineering theme and mechanobiology group are jointly hosting a seminar on 'Mechanobiology of cellular senescence and ageing' from Dr Joe Swift from the Wellcome Centre for Cell-Matrix Research.

Title:

Mechanobiology of cellular senescence and ageing

Bio:

Joe Swift - Wellcome Centre for Cell-Matrix Research, University of Manchester

Joe received an MSci degree in chemistry with first-class honors from Imperial College, completing project work under Prof. Richard Templer on the phase changes of liquid crystals. He then continued his studies in the USA and was an awarded a PhD in chemistry from the University of Pennsylvania in 2008. His thesis explored the re-engineering of ferritin proteins to act as scaffolds for nanoparticle formation, work undertaken with the guidance of Prof. Ivan Dmochowski.

Joe then stayed in Philadelphia to work with Prof. Dennis Discher, developing proteomic methods to study the nucleoskeletal lamin proteins and their roles in mechanotransduction. In 2014, he was awarded a BBSRC David Phillips Fellowship to develop his own program of research at the University of Manchester.

Abstract:

Tissues are maintained by homeostatic feedback mechanisms in which cells can respond to, but also modify, the chemical and mechanical properties of the surrounding extracellular matrix (ECM). Mechano-sensitive mesenchymal stromal/stem cells (MSCs) resident in the marrow niche experience a diverse mechanical environment, but ageing can affect the composition and quality of bone and marrow tissues. Senescence is a protection mechanism against uncontrolled proliferation, but senescent cells accumulate in ageing tissues as they are no longer effectively removed by the immune system. As well as reducing the capacity of tissues for regeneration, the accumulation of senescent cells has negative effects on tissue function, for example by secreting inflammatory factors.

Previous work from my laboratory has shown that proliferating (i.e., non-senescent) MSCs are able to rapidly and reversibly remodel their proteomes when challenged with mechanical stress, for example to break protein linkages between the nucleus and cytoskeleton. However, new results show that replicative senescence in MSCs leads to significant loss of chaperone proteins responsible for maintaining the cytoskeleton. Furthermore, senescent MSCs lack the translational capacity to rapidly remodel their proteomes in response to stress, even when transcriptional responses are functional. These mechanisms are compounded to give senescent MSCs a blunted response to their environments, evidenced by changes to morphology and their ability to remodel the surrounding ECM.

As the potential of MSCs to be used in regenerative medicine continues to be explored, this work shows how our ability to direct cell behaviour is affected by cell replication, senescence and ageing.