91影视

As normal cells age they can only go through a finite number of cell divisions. Once they have achieved this they become irreversibly growth arrested known as replicative senescence. The transcriptome and epigenome are altered in senescent cells, as is the nuclear organisation and function. Can these mechanisms and structures be interfered with to work towards reversing
senescence and inducing cells to re-enter the proliferative cell cycle?

Initially the candidate will study differences between different types of growth arrest i.e. quiescence, stress induced premature senescence and replicative senescence using super-resolution bioimaging, chromatin analysis, transcriptome and genome behaviour. Senescent cells will be induced to replicate again by altering their access to specific factors – these replicating senescent cells will also be compared to the other arrested cells. Strategies will be developed to push these cells further to enter mitosis and divide.

Supervisors:

• Dr Ian Kill

HGPS is a premature ageing syndrome that affects children leading to their premature death in their teens through heart attacks and strokes. There have been a few drugs that have been given to the children through clinical trials and more planned. However, not very much is known about how these drugs affect the genome biology. We have investigated some of the drugs in use for the treatment of progeria and have mixed effects on the genome of these drugs. It is obvious that some new better treatments are required. 

The project will involve the testing of newly proposed drugs on genome behaviour in HGPS cells. These assays will include chromosome positioning, gene and chromosome movement, genomic instability, the epigenome, association with specific structures and transcription profiles. A range of techniques will be used such as super-resolution bioimaging, fluorescence in situ hybridisation, real-time PCR, chromatin immuno-precipitation and sequencing. Furthermore, you will be part of a team working on new treatments using state-of-the-art applications involving nanotechnology and gene therapy that will also form part
of your PhD thesis.

Supervisors:

• Dr Ian Kill

There has been a small amount of evidence in the literature that growing cells in 3D scaffolds instead of 2D monolayers alters genome behaviour and organisation such that nuclear structure is altered and consequently chromosome behaviour. Understanding such changes i.e. chromosome and gene position, nuclear structure organisation and function, chromatin movement and chromatin modification (epigenome) will provide greatly needed data to the cell biology field on whether to change their cell culture habits.

The project will involve growing young and aged cells in different 3D matricies to ask whether chromosome and gene position is altered, is the epigenome and the transcriptome affected and what happens to nuclear structures that anchor and influence chromosomes such as nucleoli, nuclear lamins, the LINC complex, the nucleoskeleton and how genes and chromosomes are moved after external stimuli such as changes to temperature and availability of nutrients. A range of techniques will be used such as super-resolution bioimaging, real-time imaging, fluorescence in situ hybridisation, real-time PCR, chromatin immuno-precipitation and sequencing.

Supervisors:

• Dr Ian Kill