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The role of dosage sensitive genes in aneuploid phenotypes
(Massachusetts Institute of Technology, 2016)
Aneuploidy-the gain or loss of one or more whole chromosomes-typically has an adverse impact on organismal fitness, manifest in conditions such as Down syndrome. A central question is whether aneuploid phenotypes are the ...
Identifying the requirement and mechanism of the dynamic yet kinetically stable ClpXP interface
(Massachusetts Institute of Technology, 2017)
AAA+ (ATPases Associated with various cellular Activities) proteases carry out regulated degradation and protein quality control. To achieve these goals, a barrel-shaped peptidase, with active sites in a sequestered chamber, ...
Productivity, metabolism and physiology of free-living Chemoautotrophic Epsilonproteobacteria
(Massachusetts Institute of Technology, 2016)
Chemoautotrophic ecosystems at deep-sea hydrothermal vents were discovered in 1977, but not until 1995 were free-living autotrophic Epsilonproteobacteria identified as important microbial community members. Because the ...
Characterization of the two major merlin isoforms and merlin regulation of YAP
(Massachusetts Institute of Technology, 2015)
Merlin is the protein encoded by the tumor suppressor gene NF2. Deletion or loss-of-function of NF2 leads to neurofibromatosis type 2, a disease characterized by the formation of multiple benign tumors of the nervous system. ...
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 ...
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, ...