Tristan Rodriguez

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Regulation of cell fitness by cell competition during early mouse development

 

Abstract: 

During the early stages of mammalian embryonic differentiation a vast array of cellular changes take place, including a dramatic increase in the proliferation rate and a rewiring of the transcriptional, epigenetic, metabolic and signalling networks. The dimension of these changes and the requirement for their timing to be carefully orchestrated implies that stringent quality control mechanisms must be in place to ensure the elimination of aberrant cells prior to the specification of the germline. Here I will discuss the work my laboratory has done to unravel the mechanism of elimination of non-lethally damaged cells during differentiation. I will present evidence to show that during embryonic differentiation, cells with mild forms of cellular damage, such as mis-patterning or karyotypical abnormalities are recognised as a less-fit by their neighbours that induce the elimination of these damaged cells. I will discuss how during this process the interplay of p53 and mTOR signalling governs the competitive interactions that ensue between cells with different fitness levels, as well as the implications of these interactions for the growth and patterning of the developing embryo.

Biography

Tristan Rodriguez is a Reader in Cell and Developmental biology in the cardiac function section of the National Heart and Lung Institute (NHLI), Imperial College London. Tristan did his PhD at the National Institute for Medical Research (London, UK) on mouse genetics and then moved to the laboratory of the late Dr. Rosa Beddington to work as a post-doctoral fellow in developmental biology. In 2002 he was awarded a Lister Institute of Medicine non-clinical fellowship to work on axis specification in the mouse embryo and moved to the MRC Clinical Sciences Centre. In 2011 the Rodriguez laboratory moved to NHLI where the research of his group focuses on understanding the mechanisms that control cell fitness.  Specifically, the Rodriguez group studies the selective pressures that act to remove suboptimal cells from the mammalian embryo. We analyse both the cell intrinsic determinants of cell fitness with a specific focus on the mitochondria, as well as the cell non-autonomous mechanisms that regulate cell fitness. Much of the latter efforts are aimed at understanding the regulation of embryonic growth by competitive cell interactions. We also study the importance of cell competition for normal tissue repair and how it can by-passed during cancer.