This presentation shared insights into MSD’s work on early drug target discovery and biomarker identification, particularly in the field of neuroscience. The presentation began with an overview of the London neuroscience programme, which focused on identifying and validating novel targets in cellular senescence using multi-omics data. Wei discussed the importance of cellular senescence in neurodegenerative diseases, explaining that senescence occurs when cells are stressed and stop proliferating, leading to altered functions and the accumulation of senescent cells. This process contributed to tissue dysfunction and age-related diseases.
The London Discovery Centre, dedicated to studying mechanisms to slow ageing, identified several mechanisms associated with ageing, including ER stress, autophagy, mitochondrial dysfunction, and cellular senescence. Wei focused on cellular senescence, highlighting its significance in neurodegenerative diseases and the therapeutic strategies to target senescent cells. The team established in vitro assays to induce senescence in primary astrocytes and characterised the senescent cells using high-throughput sequencing techniques. The omics data revealed distinct profiles of senescence markers at different stages of astrocyte development.
Wei also discussed the integration of internal omics data with human datasets to generate gene lists for senolytics and SASP-related genes. The team designed CRISPR screens to validate these gene lists, identifying hits from image and cytokine assays. Additionally, Wei introduced a natural language processing (NLP)-powered literature review platform developed in collaboration with the IT NLP team to streamline the literature review process. This tool helped prioritise genes for functional validation by extracting key information from hundreds and thousands of papers.
Wei concluded by summarising the team's efforts to accelerate target identification by integrating various data sets, collaborating with academic and industry partners, and developing advanced computational tools and AI/ML techniques.
