Publication Highlights: May 2021
Androgen-deprivation therapy (ADT) is the standard of care for the treatment prostate cancer that cannot be removed by surgery. ADT is highly effective; however, many patients go on to relapse. Here, recent PhD graduate Rafael Sanchez Martinez and co-authors have used a proteomic analysis of prostate cancer models to reveal that distinct molecular mechanisms, include amino acid and fatty acid metabolism, affect the way tumours respond to ADT (SLFN5 regulates LAT1-mediated mTOR activation in castration-resistant prostate cancer). In particular, they found that a gene called Schlafen family member 5 (SLFN5) was involved in disease recurrence, and importantly, depletion of SLFN5 strongly inhibited the growth of tumours that had returned following ADT.
The vasculature is a major part of the gut. However, its role in the day-to-day maintenance of the gut is largely unexplored. Here (Dynamic adult tracheal plasticity drives stem cell adaptation to changes in intestinal homeostasis in Drosophila), postdoc Jessica Perochon and group leader Dr Julia Cordero, together with fellow authors, have used fruit flies to uncover a previously unrecognised crosstalk between stem cells in the gut and the fruit fly’s tracheal system (which is akin to our own vasculature). Importantly, this crosstalk is essential for gut regeneration.
Our Drug Discovery Unit uses ‘fragment-based drug design’ to identify fragments that could form the basis of new drugs to treat cancer. Alan Bilsland and others within the Drug Discovery Unit have used artificial intelligence and machine learning to generate a new fragment library (Automated Generation of Novel Fragments Using Screening Data, a Dual SMILES Autoencoder, Transfer Learning and Syntax Correction). They achieved this using SMILES (simplified molecular-input line-entry system) and chemical fingerprints from a set of 486,565 commercially available fragments.
Clonal haematopoiesis of indeterminate potential (CHIP) occurs when a subset of our blood stem cells gain mutations that increase their ‘fitness’, i.e. that allow them to outgrow their fellow stem cells. CHIP is associated with increased risk of developing leukaemia, as well as heart disease and stroke. By analysing the effects of mutations over a 12-year timespan, Kristina Kirschner and fellow authors have shown that gene-specific effects contribute to stem cell fitness (Longitudinal dynamics of clonal hematopoiesis identifies gene-specific fitness effects). Importantly, this holds potential for personalising the clinical management of people with CHIP in the future.