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Functional and structural studies of AAA+ proteases
(Massachusetts Institute of Technology, 2016)
AAA+ proteases are found in all domains of life. They degrade misfolded proteins as well as specific regulatory factors and thus play critical roles in protein quality control and numerous cellular processes. These enzymes ...
Discovering regulators of the amino acid sensing pathway of mTORC1
(Massachusetts Institute of Technology, 2017)
The mechanistic target of rapamycin complex I (mTORC1) protein kinase functions as a master regulator of growth, and its deregulation is common in human disease, including cancer and diabetes. mTORC1 integrates multiple ...
Development and characterization of immunogenic genetically engineered mouse models of pancreatic cancer
(Massachusetts Institute of Technology, 2020)
Insights into mechanisms of immune escape have fueled the clinical success of immunotherapy in many cancers. However, pancreatic cancer has remained largely refractory to checkpoint immunotherapy. To uncover mechanisms of ...
The persistence of haploinsufficiency and its role in genome evolution
(Massachusetts Institute of Technology, 2020)
In diploid organisms there are two copies of every gene, one from each parent. While the majority of genes are robust to deletion of one of the two copies, a subset of genes remains highly dosage sensitive, causing a ...
Patterns of linkage disequilibrium in the human genome
(Massachusetts Institute of Technology, 2002)
Although enormous progress has occurred in the field of human genetics, the cloning of complex trait mutations remains a challenging and unresolved process. This continuing difficulty is responsible for an ever-increasing ...
Roles for the polycomb group protein BMI1 in lung adenocarcinoma progression and maintenance
(Massachusetts Institute of Technology, 2016)
The B lymphoma Mo-MLV insertion region 1 homolog (Bmil) protein is implicated as an oncogene in a variety of human cancers. During normal development, Bmil acts as part of a transcriptional repressive complex that regulates ...
The biochemical basis for the cooperative action of microRNAs
(Massachusetts Institute of Technology, 2020)
In metazoans, microRNAs (miRNAs) act to repress mRNAs through a combination of translational repression and target degradation. miRNAs predominantly pair within the 3' untranslated region (3' UTR) of the mRNA. In cells, ...
Horizontal gene transfer as a cohesive force in microbial populations
(Massachusetts Institute of Technology, 2017)
Populations are the central unit of evolution and ecology. In the context of evolution, populations are commonly defined as groups of organisms with a shared gene pool in which adaptive genes can spread freely through ...
Mechanisms of CipS reprogramming of the AAA+ protease CipAP
(Massachusetts Institute of Technology, 2016)
The proteome of a cell needs to be constantly modified for protein quality control and to respond to environmental and developmental changes. Energy-dependent proteases are key to ensuring the proper composition of the ...
Molecular organization of the actin cortex in apical constriction and epithelial folding
(Massachusetts Institute of Technology, 2017)
Actin and myosin generate contractile forces to change tissue and cell shape. These shape changes are essential for many biological functions, ranging from muscle contraction to tissue morphogenesis in development. While ...