Decoding Gene Activation: Insights from Long-Read Single-Cell Sequencing

Prof Adam Cribbs; University of Oxford

Adam leads a computational biology team with a focus on systems biology, immunology, and epigenetics. His research integrates advanced computational methods, including machine learning, with functional genomics and experimental biology to address critical questions in disease biology. Adam earned his Ph.D. in molecular T cell immunology from Imperial College London in 2013. He subsequently joined the University of Oxford as a postdoctoral scientist, where he investigated the epigenetic regulation of T cell activation. This was followed by a unique 3-year MRC Fellowship in Computational Biology with Prof Chris Ponting at the University of Oxford, focusing on the development of computational approaches to understand complex biological systems. Upon completing this fellowship, Adam was appointed as a group leader in Computational Biology and MRC Career Development Fellow at the Botnar Research Centre, also within the University of Oxford. The Cribbs lab is dedicated to creating a comprehensive digital atlas of healthy cellular states in the immune and musculoskeletal systems. This atlas serves as a critical resource for identifying molecular and cellular deviations in disease, enabling the lab to uncover actionable mechanisms to restore normal cellular function. Through the integration of computational modelling, genomics, and cutting-edge experimental techniques, the lab aims to advance our understanding of disease processes and inform the development of novel therapeutic strategies.

We have developed advanced single-cell long-read sequencing assays that address the biases and errors that have plagued the adoption of long-read methods. These assays enable accurate profiling of gene regulation and splicing at single-cell resolution. Leveraging this technology, we have established comprehensive atlases of healthy musculoskeletal and immune states, providing critical references. By mapping disease states, including multiple myeloma, onto these profiles, we have identified novel therapeutic targets, particularly those involving splicing dysregulation, offering new opportunities for precision medicine.