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Alban Ordureau develops novel technique to observe ubiquitylation events - May 04, 2018

Alban Ordureau, a postdoc in the Harper lab, has developed a proteomics method that allows for the dynamics of PARKIN-dependent mitochondrial ubiquitylation to be followed with unprecedented preision and in a site-specific manner. The approach employed targeted proteomics of ubiquitylation sites in 15 PARKIN targets, allowing digital snapshots of PARKIN activity. This system was used to monitor PARKIN activity in stem cell-derived cortical and dopaminergic neurons, and to examine mechanistic aspects of the pathway.

This work was published in Molecular Cell (April 19th, 2018 issue). To learn more, see HMS News.

Kirchhausen lab develops new microscope that captures 3-D movies of cells inside living organisms - Apr 22, 2018

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The Kirchhausen lab, in collaboration with Nobel laureate and Janelia group leader Eric Betzig, has developed a microscope capable of capturing 3-D images and videos of cells inside living organisms in unprecedented detail. To enable such high resolution images, researchers combined two technologies: lattice light sheet microscopy, which Betzig developed in the early 2010s, and adaptive optics, a technique borrowed from astronomy. This work was published in a new study in the April 20, 2018 issue of Science. To learn more, read here.

Wade Harper named as a Fellow of the American Academy of Arts and Sciences - Apr 22, 2018

Wade Harper

Dr. Wade Harper, Chair of Cell Biology and the Bert and Natalie Vallee Professor of Molecular Pathology, was just named a 2018 Fellow of the American Academy of Arts and Sciences.  The mission of the Academy is to champion scholarship, civil dialogue, and useful knowledge.  It is one of the country’s oldest learned societies and independent policy research centers, and it convenes leaders from the academic, business, and government sectors to respond to the challenges facing the nation and the world.  Other notables named to this year's class include several Harvard-affiliated researchers, as well as Barack Obama and Sonia Sotomayor!  Congrats to Wade!

Nicholas Bodnar wins prestigious Harold M. Weintraub Graduate Student Award! - Apr 05, 2018

Nick Bodnar

Nick Bodnar, an MD/PhD student from the Rapoport lab, was one of 13 graduate students selected to receive a 2018 Harold M. Weintraub Graduate Student Award, which recognizes outstanding achievement in graduate studies in the biological sciences. Winners were selected based on the quality, originality, and significance of their work. Nick is a member of the HMS Biological and Biomedical Sciences graduate program.  Congratulations Nick!

Through a systematic analysis of ribophagy in mammalian cells, the Harper lab defines how ribosomes and other cytosolic proteins are eaten via autophagy in response to stress - Jan 02, 2018

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Ribosomes are abundant cellular machines regulated by assembly, supernumerary subunit turnover, and nascent chain quality control mechanisms. Moreover, nitrogen starvation in yeast has been reported to promote selective ribosome delivery to the vacuole in an autophagy conjugation system-dependent manner, a process called "ribophagy". However, whether ribophagy in mammals is selective or regulated has not been examined. Using Ribo-Keima flux reporters, Heeseon An from the Harper lab, in a recent lab report in Nature Cell Biology, found that starvation or mTOR inhibition promotes VPS34-dependent ribophagic flux, which unlike yeast, is largely ATG8 conjugation independent and occurs concomitantly with other cytosolic protein autophagic flux reporters, indicating the absence of selectivity in this process. Ribophagic flux was not induced upon inhibition of translational elongation or nascent chain uncoupling, but was induced in a comparatively selective manner upon proteotoxic stress via arsenite or chromosome mis-segregation dependent upon VPS34 and ATG8 conjugation. Unexpectedly, Heeseon found that agents typically used to induce selective autophagy also promoted increased ribosome and cytosolic protein reporter flux, suggesting significant bulk or "by-stander" autophagy during what is often considered selective autophagy. These results emphasize the importance of monitoring non-specific cargo flux when assessing selective autophagy pathways.

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