Regulation of growth and metabolism

Lead Research Organisation: The Francis Crick Institute

Abstract

We study how environmental stresses during early life can alter the way our body develops and functions in health and disease.
Developing and growing animals can adapt to tolerate moderate levels of environmental stresses such as malnutrition and lack of oxygen. We focus on identifying new genes responsible for the underlying stress-protective mechanisms.
These genes can then be manipulated with the therapeutic aim of de-stressing cells in vital organs such as the brain.
In the context of cancer, the protective genes can also be manipulated with the opposite therapeutic aim of increasing stress in tumour cells in order to kill them.
Much of our research utilizes the fruit fly Drosophila because it is quick and powerful for gene discovery and it shares more than two-thirds of all disease genes with humans.
We have used Drosophila to identify two groups of genes, also found in humans, which are essential for the brain to tolerate malnutrition and lack of oxygen. We now need to test how well these genes work in human cells before their therapeutic potential can then be developed.

Technical Summary

This work was supported by the Francis Crick Institute which receives its core funding from the UK Medical Research Council (FC001000), the Wellcome Trust (FC001000),and Cancer Research UK (FC001000)

Our research focuses on identifying the protective mechanisms that allow developing and adult animals to cope with environmental challenges such as malnutrition and hypoxia. This research also aims to shed light on the complex interactions between environmental factors and the genes influencing metabolic and age-related diseases. Much of our research utilises the fruit fly Drosophila, a model organism that shares many genes with humans and has contributed to our understanding of several different aspects of health and disease. We are also following up some of our most significant Drosophila findings in mammalian models. The laboratory uses a wide variety of experimental approaches including genetics, confocal microscopy, imaging mass spectrometry and metabolomics.
Current research in our laboratory has three specific research objectives. First, to identify intercellular signalling mechanisms that safeguard the organs of developing organisms against dietary stresses such as malnutrition. Second, to identify the mechanisms by which lipid metabolism can protect organs against oxidative stresses during development, cancer and metabolic diseases. And third, to improve techniques such as mass spectrometry imaging for the study of metabolism with unprecedented subcellular resolution.

Publications

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