Talks

Alterations in nuclear and chromatin organization are hallmarks of cellular aging and many aging related diseases including cancer and neurodegeneration. However, quantitative methods to analyse subtle alterations in chromatin states to understand cell-state transitions and for early disease diagnostics are still missing. In this talk, I will first describe our AI-based chromatin imaging biomarker platform. I will then demonstrate the sensitivity of this platform to trace tumour progression and neurodegeneration using tissue biopsies. Furthermore, I will describe our ongoing clinical trials, using AI-based chromatin biomarkers in blood biopsies, for early disease diagnostics and for tracing the efficacy of therapeutic interventions in personalized and precision medicine. Finally, I will introduce a major global public health project that we have initiated to develop a chromatin imaging atlas of human blood cells in health and disease.

It is well established that chromosome territories are non-randomly organized in the interphase nucleus, with gene poor chromosome territories proximal to the nuclear periphery, while gene rich chromosome territories are closer to the nuclear center. Such an organization is conserved in evolution. We showed that the depletion of the nuclear envelope proteins i.e, lamins, not only induces chromosomal instability but also destabilizes chromosome positioning in otherwise diploid colorectal cancer cells. Remarkably, the combined loss of lamins and Emerin perturb chromosome territory and gene loci dynamics in the interphase nucleus. Furthermore, nuclear envelope proteins are essential for relaying mechanical signals into the nucleus, since cells cultured on softer substrates showed a striking change in the spatial organization of chromosome territories in an Emerin-Lamin dependent manner. Taken together, our studies reveal an overarching role for nuclear envelope proteins, in the maintenanc...

3D organization of eukaryotic genomes scales from nucleosomes to loops, chromatin domains and chromosome territories. Given the hierarchical nature of this organization we explored the dependence of higher order genome organization on nucleosome positioning across the genome. I will discuss the mechanism by which ATP-dependent chromatin remodeller, ISWI slides nucleosomes to position them regularly and what are the consequences of perturbing nucleosome positioning across the genome on higher order genome organization.

Causal reasoning is vital for effective reasoning in many domains, from healthcare to economics. In medical diagnosis, for example, a doctor aims to explain a patient’s symptoms by determining the diseases causing them. This is because causal relations, unlike correlations, allow one to reason about the consequences of possible treatments and to answer counterfactual queries. In this talk I will present some recent work done with my collaborators about how one can learn and reason with counterfactual distributions, and why this is importantly for decision making. In all cases I will strive to motivate and contextualise the results with real word examples.