Exploring nuclear heterogeneity in the senescence tumour suppressor response combining microfluidics based phenotyping and single cell genomics

 

Project description

Project Description

Every cell in our body has the same genetic information, yet different cells display distinct features, which often allow them to perform unique tasks. This “specialisation” of cells is achieved by activating a unique combination of genes, collectively known as transcriptome. Cells with similar transcriptomes often display similar features and behaviour. Studying connection between transcriptome and appearance has not been feasible for two main reasons: A) There is no automated way to collect individual cells based on appearance. B)  Measuring the transcriptome in single cells has only been achieved. We will develop an instrument which can take a mix of cells, isolate cells based on visual features and record their transcriptome. Knowing both, how the cell looked and its transcriptome will present a milestone in investigating the relationship between gene expression and particular visual properties of cells. We will study the changes in the nuclei of cells when they become senescent - a process by which cells stop dividing to escape a cancer-inducing stimulus. Importantly, cellular senescence also plays a poorly understood role in ageing. The DNA in some senescent cells can rearrange to form a visual pattern. However, the causes and function of such rearrangements are still unknown and difficult to investigate as it is only some of the cells which display the changes. Isolating cells based on DNA arrangement will enable us to find what makes these cells different from their companions, which will provide critical insight into the cellular changes in cancer suppression and ageing.