Activity- and reactivity-based proteomics: Recent technological advances and applications in drug discovery.

Activity-based protein profiling (ABPP) is recognized as a powerful and versatile chemoproteomic technology in drug discovery. Central to ABPP is the use of activity-based probes to report the activity of specific enzymes or reactivity of amino acid types in complex biological systems. Over the last two decades, ABPP has facilitated the identification of new drug targets and discovery of lead compounds in human and infectious disease.

CRISPR-TAPE: protein-centric CRISPR guide design for targeted proteome engineering.

Rational molecular engineering of proteins with CRISPR-based approaches is challenged by the gene-centric nature of gRNA design tools. To address this, we have developed CRISPR-TAPE, a protein-centric gRNA design algorithm that allows users to target specific residues, or amino acid types within proteins. gRNA outputs can be customized to support maximal efficacy of homology-directed repair for engineering purposes, removing time-consuming post hoc curation, simplifying gRNA outputs and reducing CPU times.

FSP1 is a glutathione-independent ferroptosis suppressor.

Ferroptosis is an iron-dependent form of necrotic cell death marked by oxidative damage to phospholipids. To date, ferroptosis has been thought to be controlled only by the phospholipid hydroperoxide-reducing enzyme glutathione peroxidase 4 (GPX4) and radical-trapping antioxidants. However, elucidation of the factors that underlie the sensitivity of a given cell type to ferroptosis is crucial to understand the pathophysiological role of ferroptosis and how it may be exploited for the treatment of cancer.

Activity based chemical proteomics: profiling proteases as drug targets.

The pivotal role of proteases in many diseases has generated considerable interest in their basic biology, and in the potential to target them for chemotherapy. Although fundamental to the initiation and progression of diseases such as cancer, diabetes, arthritis and malaria, in many cases their precise role remains unknown. Activity-based chemical proteomics-an emerging field involving a combination of organic synthesis, biochemistry, cell biology, biophysics and bioinformatics-allows the detection, visualisation and activity quantification of whole families or selected sub-sets of proteases based upon their substrate specificity.