Overview
The Cellular Genomics Programme is seeking a highly motivated staff scientist to lead wet lab work in the Lee-Six group. The group is focused on studying the earliest stages of childhood cancer by investigating the conditions under which cells with particular cancer-driving mutations gain a selective advantage over their healthy neighbours. The applicant will have the opportunity to be embedded in a large community of experimental and computational scientists with access to world-leading computational and experimental facilities at the institute.
About the Team
Henry Lee-Six is a paediatric pathology registrar. His previous work has been focused on somatic mutations in normal tissues. He is starting a new group in the Cellular Genomics Programme with the aim of understanding the interplay of somatic mutations and development in childhood cancer. A major goal of the group is to investigate the relative contribution of mutation identity, cell state, and microenvironmental context in determining whether a mutant cell progresses to form a tumour. The group pursues this line of research by studying samples of children's tumours and normal tissues with cutting-edge spatial transcriptomic platforms coupled to different mutation-calling technologies such as laser capture microdissection and duplex sequencing. These data are used to build models of what determines a cell's selective advantage, which are in turn queried to suggest perturbations to a cell's state or microenvironment that might change the relative fitness of a mutant clone. These in silico predictions are then tested in vitro using iPSC and cell-line models. The group is a mixture of wet and dry lab researchers and clinicians and collaborates closely with other teams in the Cellular Genomics Programme and the wider Institute.
About the Role
You will use CRISPR-Cas9 to generate genotypes of interest in human iPSC lines, differentiate them into cell states of interest, and characterise their behaviour using a combination of methods, including transcriptomic analysis and functional assays of proliferation and death. In due course you will design and execute more complex culture systems, including co-culture. You will work closely with computational members of the team, and will collaborate with other teams within the Institute and beyond. You will contribute to the day-to-day supervision of students.
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