The Opportunity:
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.