Immunology

Ribosomes—macromolecular machines consisting of RNA and proteins that twist, fold and turn—are responsible for making all of the protein within a cell, but because they assemble so speedily, researchers haven’t been able to figure out how they come together. As part of a collaboration between Salk and The Scripps Research Institute, co-senior author Dmitry Lyumkis, a Helmsley-Salk Fellow, deployed a cutting-edge imaging method called single-particle cryo-electron microscopy (cryo-EM) and accompanying analysis tools to decipher some of the key steps for how ribosomes are assembled, a first step in understanding their roles in health and disease. The results appeared online December 1, 2016, in the journal Cell.

Helmsley-Salk Fellow and senior author Dmitry Lyumkis, first author Dario Passos and collaborators have solved the atomic structure of a key piece of machinery that allows HIV to integrate into human host DNA and replicate in the body. The findings about this machinery, known as the “intasome,” appeared January 6, 2017, in Science and yield structural clues informing the development of new HIV drugs.

Normally when we think of viruses, from the common cold to HIV, we want to boost people’s immunity to fight them. But for scientists who develop therapeutic viruses (to, for example, target cancer cells or correct gene deficiencies) a more important question is: How do we keep people’s natural immune responses at bay? In these cases, an overenthusiastic immune response actually undermines the therapy. Salk Associate Professor Axel Nimmerjahn and first author Yusuf Tufail—along with Associate Professor Clodagh O’Shea, Professor Greg Lemke and colleagues— discovered that inhibiting a protein called phospholipid scramblase 1 (PLSCR1) controls the infected cell’s antiviral response and provides long-term protection from immune attack and excessive inflammation. The results, described in the January 19, 2017, issue of Neuron, hold promise both for virally delivered treatments and inflammatory conditions like infections, autoimmune disorders such as lupus, or neurodegenerative diseases such as Alzheimer’s.