New research from the Zaia laboratory has been published in Molecular Proteomics: "Why glycosylation matters in building a better flu vaccine".
Low vaccine efficacy against seasonal influenza A virus (IAV) stems from the ability of the virus to evade existing immunity while maintaining fitness. While most potent neutralizing antibodies bind antigenic sites on the globular head domain of the IAV envelope glycoprotein hemagglutinin (HA), the error-prone IAV polymerase enables rapid evolution of key antigenic sites, resulting in immune escape. Significantly, the appearance of new N-glycosylation consensus sequences (sequons, NXT/NXS, rarely NXC) on the HA globular domain occurs among the more prevalent mutations as an IAV strain undergoes antigenic drift. The appearance of new glycosylation shields underlying amino acid residues from antibody contact, tunes receptor specificity, and balances receptor avidity with virion escape, all of which help maintain viral propagation through seasonal mutations. The determination of site-specific glycosylation of IAV glycoproteins would enable development of vaccines that take advantage of glycosylation-dependent mechanisms whereby virus glycoproteins are processed by antigen presenting cells
A recent publication in Nature Methods by Hu et al. from the Emili lab describes a software toolkit that enables users to infer protein complexes from elution profile-based fractionation methods. Over the last couple of years methods to identify macromolecular complexes without antibody pulldowns or affinity-purification have been described that are based on the idea to fractionate cellular protein extracts under non-denaturing conditions and to quantify the abundance profiles of the proteins across the fractions. Co-fractionating proteins are then considered to be members of the same protein complex. Inferring protein complexes from co-fractionation data is a non-trivial computational task, however. The software (‘EPIC’) helps to automate this process and simplify the discovery of protein complexes. This study describes the computational methods and an application to C. elegans in order to reveal a map of putative worm protein complexes. The novelty here is both the specific software toolkit, which is freely available online, and the global worm interactome.
Vascular endothelial growth factor receptor 2 (VEGFR2) is a heavily N-glycosylated pro-angiogenic receptor tyrosine kinase. Stimulation of the receptor by vascular endothelial growth factor (VEGF) induces quiescent endothelial cells to proliferate and sprout, and VEGFR2 signaling is also required for tumor growth and metastasis. In a new paper in the Journal of Biological Chemistry by Kevin Brown Chandler and colleagues in the Costello and Rahimi laboratories demonstrated that the glycosylation status of VEGFR2 alters signaling through the receptor. Specifically, sialic acid-capped N-glycans at site N247 oppose ligand-mediated receptor activation, whereas asialo-glycans (lacking sialic acid) favor VEGFR2 activation.
The Department wanted to share the good news that Shawn Lyons, Ph.D., has accepted our offer to join the department as an Assistant Professor as of October 1, 2019. Shawn obtained his Ph.D. in the laboratory of Dr. William Marzluff working on histone mRNA metabolism. He is currently a postdoctoral fellow with Dr. Paul Anderson at Harvard Medical School (Brigham and Women’s) working on the regulation of protein synthesis during acute stress response in cells, in particular how RNA metabolism and ribosome biogenesis are altered in response to stress. His work is extremely exciting, and will connect with that of a number of other department members, particularly those in the RNA biology group. Please join us in welcoming Shawn to the department!
Congratulations to the graduates from the Department of Biochemistry. Jessica Calloway Jones from the Farmer lab received her PhD. Neya Vishwanath who performed her research in the Layne lab received her MS in Medical Sciences degree. Neya (picture right) was also a speaker at the morning GMS graduation. Congratulations to all.
Heterotrimeric G proteins are signaling switches that control cellular communication across metazoans. From a traditional standpoint, these G-proteins are activated by G-protein-coupled receptors (GPCRs). However, a recent paper published in the Journal of Cell Biology by Arthur Marivin and colleagues provides direct evidence that heterotrimeric G-proteins can be activated in vivo by a cytoplasmic factor instead of by a GPCR. Specifically, DAPLE, a non-receptor protein bearing an evolutionarily conserved G-protein activating motif, triggers apical cell constriction during neurulation in Xenopus and zebrafish embryos via G-protein dependent signaling. This project of the Garcia-Marcos Lab was carried out in collaboration with the Dominguez Lab (Dept. of Medicine) and the Cifuentes Lab (Dept. of Biochemistry) at BU.
The Henry I. Russek Award Nominating Committee and the Russek Executive Committee would like to announce the winners of this year’s Department of Biochemistry awards. The honorable mention was awarded to Deborah Chang who is a student in Dr. Zaia’s lab, second prize was awarded to Julia Hicks-Berthet who is a student in Dr. Varelas's lab and the first prize was awarded to Elena Stampouloglou, who is a student in Dr. Varelas's lab. There is more great news for our department! The first prize awardee for the Molecular & Translational Medicine program is Rekha Raghunathan, a student in Dr. Zaia’s lab and the first prize awardee for the Genetics & Genomics program is Stefanie Chan, a student in Dr. Perissi’s lab. Congratulations to all of the awardees (and their mentors)!
So, we'll see you all this Friday, April 26th in Hiebert Lounge for Henry I. Russek Student Achievement Day 2019 and the keynote address to be delivered by Dr. Xiowei Zhuang; her talk is entitled “Illuminating Biology at the Nanoscale and Systems Scale by Imaging”.
Research on Klotho and Alzheimer's from Dr. Carmela Abraham's lab and Dr. Abraham's former trainee, Gwendolyn King, was mentioned in a New York Times article: "Turbocharge your brain".