The Broad Institute of MIT and Harvard

Cambridge, MA, United States

The Broad Institute of MIT and Harvard

Cambridge, MA, United States

The Eli and Edythe L. Broad Institute of MIT and Harvard , often referred to as the Broad Institute, is a biomedical and genomic research center located in Cambridge, Massachusetts, United States. The institute is independently governed and supported as a 501 nonprofit research organization under the name Broad Institute Inc., and is partners with Massachusetts Institute of Technology, Harvard University, and the five Harvard teaching hospitals. Wikipedia.


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Hotamisligil G.S.,The Broad Institute of MIT and Harvard
Nature | Year: 2017

Proper regulation and management of energy, substrate diversity and quantity, as well as macromolecular synthesis and breakdown processes, are fundamental to cellular and organismal survival and are paramount to health. Cellular and multicellular organization are defended by the immune response, a robust and critical system through which self is distinguished from non-self, pathogenic signals are recognized and eliminated, and tissue homeostasis is safeguarded. Many layers of evolutionarily conserved interactions occur between immune response and metabolism. Proper maintenance of this delicate balance is crucial for health and has important implications for many pathological states such as obesity, diabetes, and other chronic non-communicable diseases. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.


Grant
Agency: European Commission | Branch: H2020 | Program: CSA | Phase: INT-01-2015 | Award Amount: 2.42M | Year: 2016

The EU and the USA have highly-productive, immensely-innovative and excellence-driven research and innovation systems. Acknowledging the particular strengths of each landscape, a balanced transatlantic STI partnership of equals bears great potential and contributes to the ultimate goal of tackling societal challenges and boost economic competitiveness. International cooperation between power nodes results in a constant knowledge exchange and more efficient use of STI investment. BILAT USA 4.0s targeted transatlantic activities work towards: i) Strategic priority setting for EU-US cooperation through identifying emerging STI fields with a high benefit and added value from cooperation, thus providing evidence-based input for policy decision-making ii) Stronger interaction between EU and US researchers through thematic events promoting funding opportunities on both sides and thus strengthening the quality and quantity of partnerships between STI actors in EU MS/AC and the USA iii) Establishing optimal framework conditions through proposing concrete solutions for eliminating cooperation obstacles deriving from researchers and innovators feedback, thus, creating an environment that favors joint solutions for global challenges iv) Enhanced coordination and synergies between different policies through analyzing EU, MS/AC and US programmes and detection of duplications, thus, contributing to a greater coherence, joint ownership and resource efficiency v) Ensuring close synergies with calls launched in H2020 and their int. dimension through screening of US-targeted actions in H2020 and liaising with relevant (ERA) projects to guarantee a consistent information exchange Ensuring sustainability, project activities build on former and liaise with existing initiatives. Relevance and exploitation of project actions will be assured by a close coordination with the EC. The project will pursue a targeted communication connecting the diverse range of EU-US STI stakeholders.


Blainey P.C.,The Broad Institute of MIT and Harvard | Blainey P.C.,Massachusetts Institute of Technology
FEMS Microbiology Reviews | Year: 2013

Interest in the expanding catalog of uncultivated microorganisms, increasing recognition of heterogeneity among seemingly similar cells, and technological advances in whole-genome amplification and single-cell manipulation are driving considerable progress in single-cell genomics. Here, the spectrum of applications for single-cell genomics, key advances in the development of the field, and emerging methodology for single-cell genome sequencing are reviewed by example with attention to the diversity of approaches and their unique characteristics. Experimental strategies transcending specific methodologies are identified and organized as a road map for future studies in single-cell genomics of environmental microorganisms. Over the next decade, increasingly powerful tools for single-cell genome sequencing and analysis will play key roles in accessing the genomes of uncultivated organisms, determining the basis of microbial community functions, and fundamental aspects of microbial population biology. © 2013 Federation of European Microbiological Societies.


Wagner J.C.,The Broad Institute of MIT and Harvard
Nature methods | Year: 2014

Malaria is a major cause of global morbidity and mortality, and new strategies for treating and preventing this disease are needed. Here we show that the Streptococcus pyogenes Cas9 DNA endonuclease and single guide RNAs (sgRNAs) produced using T7 RNA polymerase (T7 RNAP) efficiently edit the Plasmodium falciparum genome. Targeting the genes encoding native knob-associated histidine-rich protein (kahrp) and erythrocyte binding antigen 175 (eba-175), we achieved high (≥ 50-100%) gene disruption frequencies within the usual time frame for generating transgenic parasites.


The inability to quantify large numbers of proteins in tissues and biofluids with high precision, sensitivity, and throughput is a major bottleneck in biomarker studies. We previously demonstrated that coupling immunoaffinity enrichment using anti-peptide antibodies (SISCAPA) to multiple reaction monitoring mass spectrometry (MRM-MS) produces Immunoprecipitation MRM-MS (immuno-MRM-MS) assays that can be multiplexed to quantify proteins in plasma with high sensitivity, specificity, and precision. Here we report the first systematic evaluation of the interlaboratory performance of multiplexed (8-plex) immuno-MRM-MS in three independent labs. A staged study was carried out in which the effect of each processing and analysis step on assay coefficient of variance, limit of detection, limit of quantification, and recovery was evaluated. Limits of detection were at or below 1 ng/ml for the assayed proteins in 30 μl of plasma. Assay reproducibility was acceptable for verification studies, with median intra- and interlaboratory coefficients of variance above the limit of quantification of 11% and <14%, respectively, for the entire immuno-MRM-MS assay process, including enzymatic digestion of plasma. Trypsin digestion and its requisite sample handling contributed the most to assay variability and reduced the recovery of target peptides from digested proteins. Using a stable isotope-labeled protein as an internal standard instead of stable isotope-labeled peptides to account for losses in the digestion process nearly doubled assay accuracy for this while improving assay precision 5%. Our results demonstrate that multiplexed immuno-MRM-MS can be made reproducible across independent laboratories and has the potential to be adopted widely for assaying proteins in matrices as complex as plasma.


Hyman S.E.,The Broad Institute of MIT and Harvard
Neuropsychopharmacology | Year: 2014

Despite high prevalence and enormous unmet medical need, the pharmaceutical industry has recently de-emphasized neuropsychiatric disorders as 'too difficult' a challenge to warrant major investment. Here I describe major obstacles to drug discovery and development including a lack of new molecular targets, shortcomings of current animal models, and the lack of biomarkers for clinical trials. My major focus, however, is on new technologies and scientific approaches to neuropsychiatric disorders that give promise for revitalizing therapeutics and may thus answer industry's concerns. © 2014 American College of Neuropsychopharmacology.


Hotamisligil G.S.,The Broad Institute of MIT and Harvard
Cell | Year: 2010

The endoplasmic reticulum (ER) is the major site in the cell for protein folding and trafficking and is central to many cellular functions. Failure of the ER's adaptive capacity results in activation of the unfolded protein response (UPR), which intersects with many different inflammatory and stress signaling pathways. These pathways are also critical in chronic metabolic diseases such as obesity, insulin resistance, and type 2 diabetes. The ER and related signaling networks are emerging as a potential site for the intersection of inflammation and metabolic disease. © 2010 Elsevier Inc.


Hyman S.E.,The Broad Institute of MIT and Harvard
Cell | Year: 2014

In the face of growing controversy about the utility of genetic mouse models of human disease, Rothwell et al. report on a shared mechanism by which two different neuroligin-3 mutations, associated with autism spectrum disorders in humans, produce an enhancement in motor learning. The open question is how much we can learn about human ills from such models. © 2014 Elsevier Inc.


Li H.,The Broad Institute of MIT and Harvard
Bioinformatics | Year: 2011

Summary: Tabix is the first generic tool that indexes position sorted files in TAB-delimited formats such as GFF, BED, PSL, SAM and SQL export, and quickly retrieves features overlapping specified regions. Tabix features include few seek function calls per query, data compression with gzip compatibility and direct FTP/HTTP access. Tabix is implemented as a free command-line tool as well as a library in C, Java, Perl and Python. It is particularly useful for manually examining local genomic features on the command line and enables genome viewers to support huge data files and remote custom tracks over networks. © The Author 2011. Published by Oxford University Press. All rights reserved.


Koehler A.N.,The Broad Institute of MIT and Harvard
Current Opinion in Chemical Biology | Year: 2010

Transcription factors with aberrant activity in disease are promising yet untested targets for therapeutic development, particularly in oncology. Directly inhibiting or activating the function of a transcription factor requires specific disruption or recruitment of protein-protein or protein-DNA interactions. The discovery or design of small molecules that specifically modulate these interactions has thus far proven to be a significant challenge and the protein class is often perceived to be 'undruggable.' This review will summarize recent progress in the development of small-molecule probes of transcription factors and provide evidence to challenge the notion that this important protein class is chemically intractable. © 2010 Elsevier Ltd. All rights reserved.

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