Dr Chwen Tay

Dysregulation of the innate immune system leads to a variety of diseases ranging from sepsis to autoinflammatory states. Previous work in the group demonstrated that regulatory genetic variation plays an important role in driving individual differences in extreme innate immune response phenotypes.

Our current aims are to characterise the functional alleles involved in causing the differences in the innate immune response. To this end, we aim to investigate the biological consequences and mechanisms of action of regulatory and coding gene variants using iPSC-derived monocytes and macrophages coupled with high-throughput CRISPR/CAS9 screens. The detailed characterisation of specific functional alleles derived from the high-throughput screens will then help define key nodal genes and pathways for therapeutic intervention and drug prioritisation, and provide further insight into fundamental processes in gene regulation and disease pathogenesis.

Background

I obtained my PhD in Molecular Biology from the Wellcome Trust Sanger Institute where I investigated the targets and role of palmitoylation in Plasmodium parasites, focusing on the DHHC-palmitoyltransferase protein family. This was followed by a Post-Doc position at Imperial College London where I used CRISPR/CAS9 techniques to characterise the function and essentiality of different P. falciparum genes at different stages of the parasite life cycle. I then moved to the NHS Blood and Transplant in Bristol where I worked on setting up CRISPR/CAS9 technology in an immortalised erythroid stem cell line with the aim of creating ‘designer’ manufactured red blood cells.

I recently joined the Knight group where I will be working on setting up high-throughput CRISPR/CAS9 screens, as well as more specific CRISPR/CAS9 modification of single gene targets and regulatory regions, in order to investigate the functional alleles involved in the extreme innate immune response.