Molecular effect of stress on depression

The effect of life stress on depression is moderated by a repeat length variation in the transcriptional control region of the serotonin transporter gene, which renders carriers of the short variant vulnerable for depression. We investigated the underlying neural mechanisms of these epigenetic processes in individuals with no history of psychopathology by using multimodal magnetic resonance-based imaging (functional, perfusion, and structural), genotyping, and self-reported life stress and rumination. Based on functional MRI and perfusion data, we found support for a model by which life stress interacts with the effect of serotonin transporter genotype on amygdala and hippocampal resting activation, two regions involved in depression and stress. Life stress also differentially affected, as a function of serotonin transporter genotype, functional connectivity of the amygdala and hippocampus with a wide network of other regions, as well as gray matter structural features, and affected individuals' level of rumination. These interactions may constitute a neural mechanism for epigenetic vulnerability toward, or protection against, depression.

Source:

Neural correlates of epigenesis. Turhan Canli et al. Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0601674103.

RNA interference wins Nobel Prize 2006

This year's Nobel Laureates have discovered a fundamental mechanism for controlling the flow of genetic information. Our genome operates by sending instructions for the manufacture of proteins from DNA in the nucleus of the cell to the protein synthesizing machinery in the cytoplasm. These instructions are conveyed by messenger RNA (mRNA). In 1998, the American scientists Andrew Fire and Craig Mello published their discovery of a mechanism that can degrade mRNA from a specific gene. This mechanism, RNA interference, is activated when RNA molecules occur as double-stranded pairs in the cell. Double-stranded RNA activates biochemical machinery which degrades those mRNA molecules that carry a genetic code identical to that of the double-stranded RNA. When such mRNA molecules disappear, the corresponding gene is silenced and no protein of the encoded type is made.

RNA interference occurs in plants, animals, and humans. It is of great importance for the regulation of gene expression, participates in defense against viral infections, and keeps jumping genes under control. RNA interference is already being widely used in basic science as a method to study the function of genes and it may lead to novel therapies in the future.

Source:
Nobel Prize in Physiology or Medicine 2006

Connectivity Map

New genomic tool makes connections between drugs and human disease.

While the ultimate goal of biomedicine is to connect each human disease with drugs that can effectively treat or cure it, the paths toward this goal are often circuitous. The earliest steps, in particular, can be hindered by a lack of basic knowledge about how drugs and diseases work — for example, the biology that underlies a particular disease or the molecules that are targeted by a drug’s action. What is needed to accelerate this “match-making” process is a relatively quick and systematic method for comparing different drugs and diseases based on their biological effects.

Toward this end, a research team led by Broad Institute scientists has developed a new kind of tool that relies on genes to connect diseases with potential drugs to treat them and to predict how new drugs function in cells. Called the "Connectivity Map," the new tool and its first uses are described in the September 29 issue of Science and in separate publications in the September 28 immediate early edition of Cancer Cell. The three papers demonstrate the map’s ability to accurately predict the molecular actions of novel therapeutic compounds and to suggest ways that existing drugs can be newly applied to treat diseases such as cancer.

Sources:
Connectivity Map : http://www.broad.mit.edu/cmap/

The Connectivity Map: Using Gene-Expression Signatures to Connect Small Molecules, Genes, and Disease. Justin Lamb et al. Science 29 September 2006: Vol. 313. no. 5795, pp. 1929 - 1935