Mechano-Genomics & AI Group at PSI, jointly with ETH-Zurich
Our research group is interested in understanding the mechano-genomics of cellular ageing and how ageing cells and ageing related disease cells, such as cancer and fibrotic cells, can be reprogrammed and rejuvenated by mechanotransduction. Towards this, we also develop novel imaging-AI based mechano-genomic biomarkers as fingerprints for cells health and disease. Our group’s research program is highly interdisciplinary and uses advanced light microscopy, microfabrication, functional genomics, theoretical modeling, and machine learning methods. On the computational side, we collaborate closely with Caroline Uhler’s group at MIT/Broad Institute. Building on our current strengths, our research is focused on two major themes:
Theme-1: Mechano-genomics of cellular aging and rejuvenation
We recently showed that mechano-chemical signals, without any exogenous factors, could induce partial programming and rejuvenation of aging cells. Using fluorescence imaging combined with genome-wide analysis, RNA-seq, and interventions our ongoing and future research are focused on identifying the molecular pathways underlying the mechanical rejuvenation of aging and aging related diseases cells. In addition, we are developing theoretical models linking chromosome packing and expression to gain mechanistic insights. Furthermore, we are exploring if such partially reprogrammed cells, implanted into human skin tissues, could provide novel cell-based therapies for ageing tissue regeneration and repair.
Theme-2: AI-based chromatin imaging biomarkers for aging related diseases
Using human tissue biopsies combined with single-cell chromatin imaging, spatial-omics and AI, our ongoing and future experiments are focused on probing the mechano-genomics of tissue reorganization during aging and aging related diseases. In collaboration with the Center for Proton Therapy at PSI and the local Health Center in Brugg, we are also exploring if subtle alterations in blood cell chromatin states induced by disease/stress secretome signals could serve as robust biomarkers for aging related diseases including cancer, metabolic disorders, and neurodegeneration. Furthermore, we are developing scalable microfluidic-based devices combined with our imaging-AI based blood cell chromatin biomarkers for large-scale field trials.
Technology transfer
Our research program on mechano-genomics and AI has also resulted in the founding of a company “FOCAL Biosciences” together with Apollo Ventures and PSI/ETH Zurich. FOCAL Biosciences aims to use our group’s know-how to develop a drug discovery platform using the “mechano-genomic principles underlying fibroblast cell-state transitions and the imaging-AI based chromatin biomarkers as robust phenotypic readouts”.
Public health project
Extending our research on AI-based chromatin imaging biomarkers, we are developing a quantitative chromatin imaging atlas of blood cells derived from healthy human donors in partnership with major blood banks. We envision that such an imaging atlas, with open access to researchers and clinicians, will provide new avenues for early diagnostics and tracing the efficacy of therapeutic interventions in personalized and precision medicine.