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Dr. Bjorn Olsen awarded 2019 King Faisal Prize in Medicine - Feb 04, 2019

Dr. Bjorn Olsen

Dr. Bjorn Olsen just received the 2019 King Faisal Prize in Medicine for his work in Bone Biology and Osteoporosis. Congratulations, Bjorn! The King Faisal Foundation works to advance King Faisal’s legacy by supporting original research that has major implications for the improvement of human health world-wide. Bjorn’s research focuses on the field of bone biology, and his findings have uncovered insights into inherited skeletal disorders, such as osteoporosis syndromes. Learn more about his research here and here.

Recent Faculty Promotion: Maofu Liao - Nov 22, 2018

Dr. Maofu Liao

Congratulations to Dr. Maofu Liao, who was just promoted from Assistant Professor to Associate Professor of Cell Biology!

Maofu's lab focuses on understanding the structure and function of membrane proteins and protein-lipid interactions made by membrane proteins such as transporters and ion channels. In particular, his lab uncovers mechanisms of how proteins sense, move, and convert specific lipid molecules. To accomplish these goals, the lab uses cryo-EM to obtain high-resolution structures of lipid-interacting proteins and is especially strong in studyig dynamic protein conformations in native membrane environments. Learn more about his lab here.

Min Luo Awarded 2018 Outstanding Postdoc Fellow Award - Nov 02, 2018

Dr. Min Luo

Congratulations to Dr. Min Luo, a postdoctoral fellow in the Liao lab, who recently received the 2018 Outstanding Postdoc Fellow Award for the Department of Cell Biology!  This award is given out annually to a postdoc in each HMS research department by the HMS/HSDM Office of Postdoctoral Fellows. Min’s research focuses on understanding the molecular mechanism of lipid-embedded molecular machines, using structure-function studies. He has been involved in multiple successful research projects, including producing the first high-resolution structure of the entire mitochondrial ATP synthase embedded in lipid membranes. This work revealed the mechanism of drug binding, and Min has followed up with related studies of human ATP synthase. The hope is that Min’s studies will lead to safer and more effective tuberculosis treatments. Additionally, Min has worked on structural and mechanistic studies of non-transmembrane proteins, the Type I CRISPR-Cas system.  By revealing how this system searches for its DNA targets, Min’s work will contribute to more efficient and accurate applications of the CRISPR system.

The Shao and Brown labs identify new ribosome-inactivating interactions - Oct 31, 2018

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The cellular activities of ribosomes, the molecular machines that synthesize proteins, regulate gene expression during many physiological processes such as blood cell differentiation. A collaboration between the Shao Lab and the Brown Lab (HMS BCMP) has identified new silencing interactions on ribosomes. Their paper in eLife computationally mined single-particle electron cryo-microscopy (cryo-EM) data of ribosomes to determine structures of inactive ribosomes containing a new tRNA binding site and protein, IFRD2. IFRD2 binds to the catalytic core of ribosomes to preclude protein synthesis. These findings provide molecular insights into how ribosomal interactions may inactivate translation to regulate gene expression.

New work from the Pellman laboratory explains defects in the nuclear envelope that give rise to a mutational phenomenon called chromothripsis - Oct 29, 2018

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Traditionally, it was assumed that cancer genomes evolve by accruing small-scale changes gradually, over many generations. However, the extreme complexity of many cancer genomes has led to an alternative view that they can evolve rapidly via discrete episodes that generate bursts of genomic alterations. One recently discovered catastrophic mutational processis called chromothripsis, which involves massive rearrangement of only one or a few chromosomes, generating an unusual DNA copy number pattern.  The mechanism for chromothripsis had not been known, but prior work from the Pellman lab established that it can originate from abnormal nuclear structures, common in cancer, called micronuclei. Micronuclei have fragile nuclear envelopes (NE, work from the Hetzer laboratory, Salk Institute) whose spontaneous “rupture”  somehow leads to chromosome fragmentation.

In the current paper in Nature, Shiwei Liu, Mijung Kwon and colleagues addressed the basis for NE fragility in micronuclei.  They found that only a subset of NE proteins properly assemble on missegregated chromsoomes that “lag” within the mitotic spindle and then form micronuclei.  The missing proteins include the nuclear pore complexes, producing nuclear transport defects in micronuclei.  This results in the failure of these structures to normally accumulate key proteins involved in NE integrity and genome maintenance.  In contrast to a previously proposed checkpoint model, the current data indicate that what inhibits the assembly of nuclear pore complexes on lagging chromosomes is the spindle microtubules themselves. Accordingly, experimental manipulations that position missegregated chromosomes away from the spindle correct defective nuclear envelope assembly, prevent spontaneous nuclear envelope disruption, and suppress DNA damage in micronuclei. The findings suggest a new model for the coordination between chromosome segregation and nuclear envelope assembly during normal mitotic exit. The data indicate that these processes are only loosely coordinated through the timing of mitotic spindle disassembly. The absence of precise checkpoint regulation explains why mitotic exit is error-prone, which can explain why chromothripsis is common. Watch this short video to learn more.

 

Yuan Lab discovers molecular link between aging and neurodegeneration - Aug 23, 2018

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The Yuan Lab has discovered a molecular link between aging and two major neurodegenerative diseases: amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Their paper in Cell illustrates how the loss of function of the proteins TBK1 and TAK1 lead to neurodegeneration in mice. Aging results in reduced levels of these proteins, thus identifying the first molecular event that associates aging with neurodegeneration. To learn more about this story, visit HMS News, Science Daily, and Medical Xpress.

Liao lab uncovers the structural basis of RNA-guided DNA degradation by Cascade and Cas3 - Aug 08, 2018

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Type I CRISPR-Cas system features a sequential target-searching and degradation process on double-stranded DNA by the RNA-guided Cascade (CRISPR associated complex for antiviral defense) complex and the nuclease-helicase fusion enzyme Cas3, respectively. The Liao lab has used single-particle cryo-electron microscopy (cryo-EM) to generate a near-atomic resolution structure of the Type I-E Cascade/R-loop/Cas3 complex, poised to initiate DNA degradation. This work, in collaboration with the Ke lab at Cornell University, was published in Science on July 6th. Together with their previous cryo-EM structures of CRISPR/R-loop (Xiao et al, Cell 2017, doi: 10.1016/j.cell.2017.06.012), their work provides a “molecular movie” that describes the entire course of action for target recognition, single strand nicking, and ATP-dependent DNA processing. The improved structural understanding now enables researchers to work toward modifying multiple types of CRISPR-Cas systems to improve their accuracy and reduce off-target effects in various biomedical applications.

Recent Faculty Promotion: Marcia Haigis - Jul 31, 2018

Dr. Marcia Haigis

Congratulations to Dr. Marcia Haigis on her promotion to Professor of Cell Biology!

Marcia's research uses biochemical, cellular, and mouse modeling approaches to systematically dissect the molecular regulation of mitochondrial functions during aging and age-related disease. In particular, her lab investigates how pathways that control aging, such as sirtuins, impact mitochondrial fuel utilization, bioenergetics and signaling. Learn more here.

Dr. Marcia Haigis selected to the Emerging Leaders in Health and Medicine Program - Jul 19, 2018

Dr. Marcia Haigis

Dr. Marcia Haigis has been selected for the National Academy of Medicine's Emerging Leaders in Health and Medicine Program. Congratulations, Marcia! The National Academy of Medicine was established in 1970 and works as a national leader to progress the field of medicine and medical policy. The Emerging Leaders in Health and Medicine Program fosters a community of leadership and innovation and chooses members based on their ability to mentor and potential to advance the future of medicine. Marcia was one in twenty named nationwide! Her lab studies the role of mitochondria in the aging process and age-related diseases. Learn more about her lab here.

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