NE-CAT News

In the arms race that is the life of bacteria, crafty microbial combatants have developed chemical weaponry that targets the cellular machinery of their enemies and kills them. For the last 100 years, scientists have studied various strains of bacteria to identify and isolate these antibiotic chemicals to be used as treatments for our own bacterial infections.

RAS proteins function as on/off switches in pathways controlling cell growth and proliferation. Mutated RASs keep the pathways permanently activated, leading to conditions such as cancer and Noonan syndrome. A protein called Leucine Zipper-like Transcription Regulator 1 (LZTR1) regulates cellular levels of RAS by promoting RAS’s destruction. However, LTZR1 is itself prone to mutations, disrupting its ability to bind and degrade RAS and causing diseases such as Noonan syndrome and Schwannomatosis.

The lab of Philip Kranzusch, Professor of Microbiology at Harvard Medical School and the Dana-Farber Cancer Institute, regularly uses beamtime at NE-CAT to examine the question of innate immunity.

Lincosamides are naturally occurring antibiotics that are effective against a variety of different types of bacterial infections. However, they possess a sulfur atom at a key location that makes them vulnerable to rapid metabolism in both animals and humans, reducing their usefulness in the clinic. Efforts to make a synthetic version without the sulfur atom have failed to generate a new antibiotic that is both long-lived and effective, and all the synthetic versions that do work still have the key sulfur. 

The human body is built for survival. Each one of its cells is closely guarded by a set of immune proteins armed with nearly foolproof radars that detect foreign or damaged DNA. One of the cells’ most critical sentinels is a “first responder” protein known as cGAS, which senses the presence of foreign and cancerous DNA and initiates a signaling cascade that triggers the body’s defenses. The 2012 discovery of cGAS ignited a firestorm of scientific inquiry, resulting in more than 500 research publications, but the structure and key features of the human form of the protein continued to elude scientists. Now, scientists at the Harvard Medical School and the Dana-Farber Cancer Institute, working at the U.S. Department of Energy’s Advanced Photon Source, have for the first time identified the structural and functional differences in human cGAS that set it apart from cGAS in other mammals and underlie its unique function in people.