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Content archived on 2024-06-18

The elucidation of the nuclear receptor gene regulatory network in mouse microglia

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The very basics of cell management

Unravelling the causes of diseases like cancer and dementia require knowledge at the atomic level in a cell. An EU-funded project is making headway in this field through a study of nuclear receptors, key molecules in cell maintenance and develop

The activation of genes so that they can make proteins is a very intricate process - a gene must be switched on at the right time in relation to other processes in a cell. One small slip and genetic and biochemical anarchy takes over, usually made obvious by the onset of disease. An EU-funded project MNRGN chose to study a certain type of white blood cell found in the brain, microglia and the way they manufacture proteins. These cells are thought to play a big part in degenerative diseases like Alzheimer's and Parkinson's as well as normal ageing. Releasing toxins, they can create a state of chaos and prevent normal message transmission in the brain. Within all cells including microglia, nuclear receptors (NRs) can sense the presence of certain hormones and other molecules. As such, they are responsible for the regulation of certain genes concerned with development, internal balance and metabolism of a cell and therefore the whole organism. Two state-of-the-art technologies were used to sort out exactly how the DNA, in conjunction with the NRs, works in these cells. Chromosome conformation capture is used to analyse the organisation of a chromosome as the cell goes about its day to day operations. High-throughput protein-DNA interaction screening helps to match genes with the proteins they code for. So far, the results of the project are very encouraging. The position and function of many genes under study have been precisely outlined. A little disappointing is that the culture system for the microglia has not been consistent. For future study, the MNGRN scientists aim to change their focus to fat cell development. The growth of a fully mature fat cell will still allow analysis of cascades of interlinked gene pathways and all the members of DNA and RNA involved in the production of proteins. As genes, their function and malfunction, are the basis of diseases like cancer and deterioration, including ageing, the outcome of this research may be very important indeed.

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