Dynamic Sorting Complex Interactions in Hormone Cancers

Steroid hormone receptors (SHRs) are an important and complex family of transcription factors whose hormone binding triggers nuclear translocation and activation of specific programmes of gene expression that facilitate different cellular processes depending on bodily location, external environment and many other factors. A huge variety of cancers come about in part from mutations in SHRs, some of them allowing activity in the absence of hormone. This project uses biomolecular engineering to biophysically investigate stability, dynamics and interactions of SHRs within a cell-free programmable microenvironment, combining in-vitro transcribed components with recombinant proteins and rabbit reticulocyte lysate. Using strategic labelling and variants, we will test the effects of different cancer-causing mutations on transcription and protein quality control machinery to understand their disease impacts. Outcomes will ultimately feed into targeted therapeutic strategies.