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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.

Whitehead Institute scientists have at last answered the long-standing question of how the growth-regulating pathway known as mechanistic target of rapamycin complex 1 (mTORC1) detects the presence of the amino acid leucine—itself a key player in modulating muscle growth, appetite, and insulin secretion.

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.

Whitehead Institute researchers have developed a tool that allows scientists to monitor changes in DNA methylation over time in individual cells. Certain diseases, including cancer, cause changes in DNA methylation patterns, and the ability to document these alterations could aid in the development of novel therapies.

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.

In the breast, cancer stem cells and normal stem cells can arise from different cell types and tap into distinct yet related stem cell programs, according to Whitehead Institute researchers. The differences between these stem cell programs may be significant enough to be exploited by future therapeutics.

Upsetting the balance between protein synthesis, misfolding, and degradation drives cancer and neurodegeneration. Recent cancer treatments take advantage of this knowledge with a class of drugs that block protein degradation, known as proteasome inhibitors. Widespread resistance to these drugs limits their success, but Whitehead researchers have discovered a potential Achilles heel in resistance. With such understandings researchers may be able to target malignancy broadly, and more effectively.

By teasing apart the structure of an enzyme vital to the parasites that cause toxoplasmosis and malaria, Whitehead Institute scientists have identified a potentially ‘drugable’ target that could prevent parasites from entering and exiting host cells.