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Dr. Jennifer Waters discusses novel fellowship program - Jan 14, 2021

Optical microscopy has become central to progress in many areas of science. At the same time, the complexity of instruments and quantitative imaging experiments has dramatically increased, with many requiring extensive expertise to operate. Microscopy facilities staffed with PhD-level imaging scientists who advise and train researchers on imaging experimental design, the best instruments to use for their experiments, and proper use of instruments have become essential sources of expertise in many research institutions, and core facility management has become a stimulating career path for scientists with experience in advanced quantitative microscopy techniques and an interest in facilitating science broadly. With the goal of helping to train the next generation of core facility imaging scientists, Jennifer Waters, Director of the Nikon Imaging Center since 2001, began the novel Advanced Microscopy Post-doctoral Fellowship Program in 2014. The program is designed to provide opportunities to develop expertise in quantitative optical microscopy and core facility management. Jennifer recently described her vision for the program in ‘A Novel Paradigm for Expert Core Facility Staff Training’, Trends Cell Biol. 30, 669–672, and was interviewed for a Nature article about core facility staff training (Core curriculum: learning to manage a shared microscopy facility, Nature 588, 358-360). Similar programs have since been developed at the Janelia Research Center and the European Molecular Biology Laboratory.

New study by Brugge Lab reveals the cellular effects of aging on the mammary gland at high resolution - Jan 14, 2021

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Aging of the mammary gland is associated with numerous changes and is linked to higher cancer risk. To better understand these changes, the Brugge lab has performed single-cell transcriptomic analysis on a mouse model to generate a high-resolution atlas of the mammary glands at young and old age. The study, published in Cell Reports, identifies altered cell proportions and gene expression in several cell types, including lesser-known populations in the epithelial and immune compartments. The results highlight patterns of functional decline as well as a shift to a pro-tumorigenic and pro-inflammatory tissue microenvironment, which may contribute to the higher breast cancer risk associated with older age.

Brugge lab identifies a “Hit-and-Run” commensal clonal interaction model leading to metastasis - Jan 05, 2021

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The extent and importance of functional heterogeneity and crosstalk between tumor cells is poorly understood. In a recent study published by Nature Communications, the Brugge lab describes the generation of clonal populations from a patien tderived ovarian clear cell carcinoma model which forms malignant ascites and solid peritoneal tumors upon intraperitoneal transplantation in mice.

The Farese/Walther lab determines that lipid droplets in brown adipose tissue are dispensable for cold-induced thermogenesis - Jan 04, 2021

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Brown fat cells help generate body heat using triglycerides stored in lipid droplets as energy, but it’s unclear whether those lipids are required. The Farese/Walther lab generated mice lacking triglycerides in brown adipose tissue by deleting enzymes that synthesize the lipids. Described in Cell Reports, the work showed that brown fat tissue is functional without triglycerides and that the triglyceride-lacking mice were able to maintain body temperature in the cold. The brown fat cells in these mice instead used circulating glucose and fatty acids and stored glycogen to fuel thermogenesis.

Rapoport lab clarifies mechanism of lamellar body formation by lung surfactant protein - Dec 03, 2020

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Pulmonary surfactant forms a thin extracellular layer that drastically reduces surface tension and is thus critical for breathing. Surfactant is initially stored in lamellar bodies (LBs) as concentric stacks of membrane layers. LB formation depends on surfactant protein B (SP-B), which is synthesized as a precursor (pre-proSP-B) and cleaved during intra-cellular trafficking into three related proteins (SP-BN, SP-BM, and SP-BC). In a recent paper in Mol. Cell, Sever et al. analyze the role of the three SP-B proteins in LB formation. Crystal structures and biochemical assays show that SP-BN is a non-specific phospholipid -binding and -transfer protein. Lipid binding to the SP-BN domain is required for vesicular export of proSP-B from the ER and neonatal viability in mice. ER export of proSP-B is also facilitated by the SP-BC domain. Once proSP-B arrives in a low-pH compartment, lipid transfer activity of the SP-BN domain is activated, resulting in the formation of lipoprotein particles and sorting of proSP-B to LBs. SP-BN is an unusual lipid transfer protein, as it moves phospholipids from a bilayer to a protein domain (SP-BM), rather than to another bilayer. Following proteolytic cleavage of proSP-B, the mature SP-BM protein generates the striking membrane layers characteristic of LBs. SP-BM alone, a protein containing only 79 amino acids, is sufficient to form these structures (see image). The only other organelle that has been reconstituted with purified proteins is the tubular ER network. Taken together, these results show how the three related SP-B domains cooperate in LB formation. 

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