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Whitehead Institute researchers have created a map of the DNA loops that comprise the three dimensional (3D) structure of the human genome and contribute to gene regulation in human embryonic stem cells. The location of genes and regulatory elements within this chromosomal framework will help scientists better navigate their genomic research, establishing relationships between mutations and disease development.

The Constitutive Centromere-Associated Network (CCAN) plays a foundational role in the machine that directs chromosome segregation during cell division. On the left is a model of the complete machine (the kinetochore) attached to the microtubule that provides the power for chromosome segregation. The right side depicts the direct interactions between CCAN sub-complexes based on Whitehead scientists’ research as viewed from above the CENP-A nucleosome, either occuring on a single nucleosome (top) or or between two nucleosomes (bottom).”

Using two complementary analytical approaches, scientists at Whitehead Institute and Broad Institute of MIT and Harvard have for the first time identified the universe of genes in the human genome essential for the survival and proliferation of human cell lines or cultured human cells. Their findings and the materials they developed in conducting the research will not only serve as invaluable resources for the global research community but should also have application in the discovery of drug-targetable genetic vulnerabilities in a variety of human cancers.

Until now, it has been difficult to fully characterize the different structures that proteins can take on in their natural environments. However, using a new technique known as sensitivity-enhanced nuclear magnetic resonance (NMR), Whitehead Institute and MIT researchers have shown that they can analyze the structure that a yeast protein forms as it interacts with other proteins in a cell.

Countering the prevailing theory that cellular hydrogen peroxide signaling is broad and non-specific, Whitehead Institute scientists have discovered that this reactive oxygen species (ROS) in fact triggers a distinct signal transduction cascade under control of the mitochondrial respiratory chain—the Syk pathway—that regulates transcription, translation, metabolism, and the cell cycle in diverse cell types. Hydrogen peroxide and other ROS mediate cellular responses in aging and myriad common chronic diseases, including diabetes, heart disease, stroke, cancer, and neurodegeneration. Understanding how these signals function may point to new therapy targets for these conditions.

A protein known to play a role in transporting the molecular contents of normal cells into and out of various intracellular compartments can also turn such cells cancerous by stimulating a key growth-control pathway.