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by R Petrosino tiennials that require a very fast reaction from the brain will have a weaker MMN/. [unreadable] This proposal is focused on the analysis of the effects of new pharmaceuticals on the mammalian circadian clock. The data collected during the first year of the proposed research are extremely promising: the mammalian circadian clock system is a fascinating and important example of a biological system that has been studied extensively and carefully on a molecular and biophysical level. In addition, the components of the circadian clock are also believed to be important in a number of human health problems. The problem of identifying and characterizing the molecular mechanisms involved in physiological processes, especially those related to human health, remains a tremendous challenge for biomedical research. The circadian clock, at least in the fruit fly, is a simple and well-studied biochemical system that is amenable to genetic analysis. Thus, the circadian clock is an ideal starting point from which to study signal transduction processes. We propose to apply research methods developed in the fruit fly and other biological systems to the identification and analysis of the transduction pathways that drive the mammalian circadian clock. Specifically, using positional cloning and DNA sequencing techniques, we will identify the genes that encode circadian clock proteins and determine the mutations that affect circadian clock function. With this information we will be able to clone the specific genes that encode mammalian circadian clock proteins and determine which of the individual proteins are the clock genes themselves. As a second major goal of this proposal, we will use "gain-of-function" experiments to test the predictions of the clockwork model of the circadian clock. That is, we will engineer the mouse to "have a day longer" or "lack a day". We will then use immunohistochemical and in situ hybridization analyses to test and confirm the predictions of the clockwork model. Finally, in vivo mutagenesis studies will be conducted to detect mutations in the mouse circadian clock. These in vivo mutagenesis studies are designed to identify specific gene(s) or even a small network of genes that are responsible for circadian rhythm generation. The genetic data collected will help in the development of drugs to help people with sleep disorders, jet lag, and shift-work problems. [unreadable] [unreadable] [unreadable]This is an archived article and the information in the article may be outdated. Please look at the time stamp on the story to see when it was last updated. Please enable Javascript to watch this video FRISCO, Texas




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