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| Why systems biology and medicine together are required for the development of novel therapeutics |
Diseases frequently arise out of an impairment of the most vulnerable feedback loop in a biological organism
Human systems are maintained at equilibrium, called Homeostasis. Homeostasis is maintained by a set of complex feedback mechanisms. For example, blood pressure and plasma cholesterol levels are maintained in a fixed range by the following mechanisms. Sensor proteins of a cell detect changes in the biological milieu, and a signal transduction mechanism transmits this information to the nucleus, where it will modify the expression pattern of genes, and hence their protein products. These proteins function as effector agents in the restoration of the original homeostasis.
Cancer and atherosclerosis are complex diseases which develop from the most vulnerable sub-systems among the many overlapping regulatory pathways. The triggering steps can originate at various points in the system landscape, and then ramify from there into the destabilizing pathology. Systems biology and medicine together are able to elucidate where the specific triggering events take place. This kind of information is priceless when it comes to pointing out the fundmanetal targets for a specifically effective drug which has minimal or no side effects. |
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Time dependent changes in gene expression and spatial changes in protein shape during signal transduction
| The human body consists of approximately 60 trillion cells. These cells are regulated by two distinct patterns of changes. The first is the time course of the expression of those 39,000 genes in the genome which have been activated. The timing of one of these expressional events is controlled exquisitely. The second critical regulatory step is the transfer of a protein and the formation of a membrane microdomain. Proteins inhabit only delimited domains of a cell, and biological signals are transmitted by the translocation and conformational change of proteins. LSBM is investigating these two critical changes at a very fine level of detail by means of DNA microarray analysis of gene expression patterns, and an antibody-based identification of the localization and conformational changes in the effector proteins. |
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A new and an epoch-making drug development target: orphan receptor genes
The Human genome encodes for many chemoreceptor genes. Because of the specificity of these pre-established pathways, chemicals which bind to these receptors can deleteriously affect the human body even at very low concentrations. Genome science now leads us to believe that there are about 5000 chemoreceptor genes in humans.
Although currently the number of proteins used for therapeutics is only 500, there could well be ten times this number among the proteins which bind the large number of as yet unidentified orphan receptors which exist. Because of its ablity to discover and functionally elucidate such receptors, LSBM enables the development of completely new therapeutics directed at previously unavailable targets. |
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