Congrats to more Cell Biology postdocs who were recently awarded prestigous fellowships! From left to right: Dr. Jennifer Rosenbluth (Brugge lab, American Cancer Society & American Society of Clinical Oncology Young Investigator Award) and Dr. Reza Behrouzi (Moazed lab, Charles A. King Trust). Dr. Alison Moreno (not shown; Haigis lab, American Cancer Society).
Congratulations to Dr. Lawrence Kazak, a postdoctoral fellow in the Spiegelman lab, who was recently awarded the American Society for Cell Biology's 2017 Merton Bernfield Memorial Award. Every year, ASCB presents the Merton Bernfield Memorial Award to an outstanding graduate student or postdoctoral member who has excelled at research. To learn more, click here.
Congratulations are in order for numerous Cell Biology postdocs who were recently awarded prestigous fellowships! From left to right: Dr. Vinay Eapen (Harper lab, Jane Coffin Child Memorial Fund); Dr. Ioannis Zervantonakis (Brugge lab, NIH K99/R00); Dr. Carman Man Chung Li (Brugge lab, Susan G Komen); Dr. Ben Orlando (Liao lab, American Cancer Society); and Dr. Brandon Wadas (Finley lab, NIH F32).
Congratulations to Dr. Wei Mi, a postdoctoral fellow in the Liao lab, who won the 2017 Outstanding Postdoc Fellow Award for the Department of Cell Biology. This award is given out annually to a postdoc in each research department by the HMS/HSDM Office of Postdoctoral Fellows. Wei's research focuses on understanding the molecular basis of lipid transport between leaflets of a cell's bilayer membrane. Specifically, he is trying to understand how certain membrane proteins, such as flippases, carry out this important cellular function. Currently, Wei is studying MsbA, a flippase found in the membranes of Gram-negative bacteria. Understanding the structure and mechanism of MsbA will be valuable in the design of antibiotics.
Cancer cells increase nutrient consumption and metabolic fitness to support rapid growth and proliferation. Consequently, the tumor microenvironment (TME) accumulates metabolic by-products, such as lactate and ammonia, which are confined due to poor vascularization of the TME. In a recent study published in Science, the Haigis lab found that the metabolic by-product ammonia accumulates in the TME of breast cancer xenograft models and has functions far beyond a metabolic waste product. The authors used stable isotope metabolic tracing studies paired with LC-MS to detect that ammonia liberated in metabolic reactions is recycled and re-incorporated into amino acids. This recycling enables a cancer cell to maximize the biosynthetic potential of their nitrogen. Furthermore, the authors found that ammonia was not toxic to breast cancer cells and accelerated their rate of growth and proliferation in vitro and in vivo. This study re-orients the notion that ammonia is a toxic metabolic by-product, and highlights a novel, biosynthetic function for ammonia in cancer.
Bob Farese has been selected as one of 14 leaders in the endocrinology field to receive a prestigious 2018 Laureate Award from the Endocrine Society. Established in 1944, these awards recognize the highest achievements in the field of endocrinology, including groundbreaking resesarch and innovations in clinical care. Bob was awarded the Roy O. Greep Award for Outstanding Research for his seminal contributions to the understanding of cellular lipid metabolism. His work has shown how alterations in lipid synthesis and storage contribute to the pathogenesis of human diseases, in particular type 2 diabetes, and has suggested new targets for therapy. Bob also pioneered the cell biology of lipid droplets, the cellular organelle responsible for storing triglycerides and metabolic energy, including identifying hundreds of genes that govern lipid storage in cells. To learn more, please click here.
Lipopolysaccharide (LPS, also known as endotoxin) in Gram-negative bacteria is critical for the bacterial survival and their resistance to antibiotics. As a critical step of LPS biosynthesis, newly produced LPS in the cytoplasmic leaflet of the inner membrane is flipped to the periplasmic leaflet by MsbA, an ATP-binding cassette transporter. In a recent study published in Nature on September 6, the Liao lab use single particle cryo-EM to obtain high-resolution snapshots of MsbA at different functional states. This study uncovers the structural basis for LPS transport, and paves the way for structural characterization of many other lipid flippases.
The Finley lab, in a recent publication in Science, found that a mutation in the murine Ube2o gene, which encodes an ubiquitin-conjugating enzyme induced during erythropoiesis, results in anemia. Proteomic analysis suggested that UBE2O is a broad-spectrum ubiquitinating enzyme that remodels the erythroid proteome. You can read more about this research in an article here on the HMS news webpage.
Proper establishment of the size of intracellular microtubule-based structures, the mitotic spindle or the cilia, is key for their cellular function. One class of mechanisms mediating size control of these intracellular structures utilizes molecular motors as “measuring devices”. Kinesin-8 motors have a conserved role in regulating the size of microtubule structures, using length-dependent accumulation at the plus-end to preferentially disassemble long microtubules. Despite extensive study, the kinesin-8 depolymerase mechanism has been debated. In a paper recently published in Developmental Cell, the Pellman lab (with first author Hugo Arellano-Santoyo) defined a tubulin curvature-sensing mechanism for Kip3/kinesin-8 depolymerization. On the straight tubulin of the microtubule lattice, Kip3 behaves like conventional motile kinesin, using ATP for processive stepping, as assayed by single molecule imaging. Upon reaching the curved tubulin of the microtubule plus-end, Kip3 undergoes a switch: Its ATPase activity is suppressed when it binds tightly to the curved conformation of tubulin. This prolongs plus-end binding, stabilizes protofilament curvature, and ultimately promotes microtubule disassembly. This tubulin-binding switch has allowed the co-existence of motility and depolymerase activity in Kip3/kinesin-8s, which is central to their ability to regulate the length of cellular microtubule structures. These findings also illustrate how small scale tuning of binding affinities and rate constants for an enzyme can generate strikingly divergent macroscopic properties.