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Seminar - Jorge Beira : Epigenetic Plasticity: Integrating signalling inputs with chromatin regulators to direct tissue regeneration or tumorigenesis

When May 02, 2018
from 03:00 PM to 04:00 PM
Where Biffen Lecture Theatre
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Dr. Jorge V. Beira from Epigenomics Group (Prof. Renato Paro), ETH Zürich, Department of Biosystems Science and Engineering will give a talk at 15:00 in the Biffen Lecture theatre on 2nd May 2018. 

Epigenetic Plasticity: Integrating signalling inputs with chromatin regulators to direct tissue regeneration or tumorigenesis

Abstract:  The diversity of cell types generated during development needs to be faithfully maintained for normal homeostatic tissue functions. How cells integrate developmental and signalling-dependent instructions to acquire or alter transcriptional states remains a fundamental question. We are investigating how developmental and signalling pathways translate into modulating chromatin states underlying distinct tissue responses. How does chromatin state balance tissue regeneration or tumour initiation?

Motivated by the parallels between the two processes, we identified context-specific features that can discriminate regenerative from tumorigenic states. Loss of Polycomb silencing triggers tumour formation in Drosophila tissues, which we used to obtain tumour transcriptomic datasets. This approach revealed deregulated pathways as well as unscheduled reactivation of embryonic genes, which we have functionally validated in vivo. We also explored the contribution of ectopic signalling pathways to promote tumour formation. We employed quantitative analyses to measure the effect of JNK, JAK/STAT and Notch pathways and uncovered two key signalling branches supporting tumour growth: JAK/STAT functions in parallel to JNK, while Notch signalling relies on JNK. We thus defined a signalling hierarchy in tumours that is distinct from the sequential activation determined during tissue regeneration.

Furthermore, we have also implemented an optimized method for tissue-specific chromatin profiling of rare cell populations. These genomic approaches overcome the current limitations of small tissue amounts (low-input ChIP), and can be generally applicable to a diverse array of organisms and developmental stages. With this complementing toolkit, we are unveiling global chromatin dynamics and enhancer reprogramming during tissue regeneration. The combination of emerging technologies with powerful genetics in a real tissue context will support further mechanistic insights driving chromatin alterations during development and homeostasis.