Protein form and function

Using tiny, alpaca-derived, single-domain antibody fragments, Whitehead Institute scientists have developed a method to perturb cellular processes in mammalian cells, allowing them to tease apart the roles that individual proteins play in these pathways. With improved knowledge of protein activity, scientists can better understand not only basic biology but also how disease corrupts cellular function and identify potential therapeutics to rectify these aberrations.

Whitehead Institute scientists have determined that a plant protein involved in the timing of flowering could in fact be a prion. This is the first time that a possible prion has been identified in plants, and it may play a role in a plant’s “memory” of cold exposure during winter.

Whitehead Institute researchers have elucidated how the growth-regulating metabolic pathway known as mTORC1 (for mechanistic target of rapamycin complex 1) senses the amino acid arginine. This nutrient sensor may represent a novel therapeutic target for controlling mTORC1, whose activity is often dysregulated in a variety of diseases, including diabetes and cancer. 

A team of researchers from Whitehead Institute and Queen Mary University of London (QMUL) have identified in follicular lymphoma tumors a mutated protein that could serve as a biomarker to predict therapeutic response.

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).”

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.