Whitehead Institute researchers have conducted the first genome-wide screen in Apicomplexa, a phylum of single-celled parasites that cause diseases such as malaria and toxoplasmosis. The screen sheds light into the vast, unstudied reaches of parasite genomes, uncovering for instance a protein common to all apicomplexans.
Whitehead Institute scientists have developed a method to quickly isolate mitochondria from mammalian cells and systematically measure the concentrations of mitochondrial metabolites. Mitochondrial dysfunction is found in several disorders, including Parkinson’s disease, cardiovascular disease, and mitochondrial diseases. Until now, peering into the inner metabolic workings of these vital organelles has been very challenging.
Whitehead Institute scientists have identified a potential antifungal mechanism that could enable combination therapy with fluconazole, one of today’s most commonly prescribed fungal infection treatments. Severe, invasive fungal infections have a mortality rate of 30-50% and cause an estimated 1.5 million deaths worldwide annually.
Whitehead Institute scientists have created a checklist that defines the “naive” state of cultured human embryonic stem cells (ESCs). Such cells provide a better model of early human embryogenesis than conventional ESCs in later stages of development.
Using tiny, alpaca-derived, single-domain antibody fragments, Whitehead Institute scientists have developed a method to perturb cellular processes in mammalian cells, allowing them to tease apart the roles that individual proteins play in these pathways. With improved knowledge of protein activity, scientists can better understand not only basic biology but also how disease corrupts cellular function and identify potential therapeutics to rectify these aberrations.
Using a novel method, Whitehead Institute researchers have determined how mutations that are not located within genes are identified through genome-wide association studies (GWAS) and can contribute to sporadic Parkinson’s disease, the most common form of the condition. The approach could be used to analyze GWAS results for other sporadic diseases with genetic causes, such as multiple sclerosis, diabetes, and cancer.
In a finding with enormous implications for cancer diagnostics and therapeutics, Whitehead Institute scientists have discovered that breaches in looping chromosomal structures known as “insulated neighborhoods” can activate oncogenes capable of fueling aggressive tumor growth.
Over the past decade, studies have found that obesity and eating a high-fat, high-calorie diet are significant risk factors for many types of cancer. Now, a new study from Whitehead Institute and MIT’s Koch Institute for Integrative Cancer Research reveals how a high-fat diet makes the cells of the intestinal lining more likely to become cancerous.
Whitehead Institute researchers have created a hydrogel scaffold that replicates the environment found within the human breast. The scaffold supports the growth of human mammary tissue from patient-derived cells and can be used to study normal breast development as well as breast cancer initiation and progression.
The germinal centers that form in the body’s lymph nodes work as a fitness boot camp in which B cells evolve to produce antibodies of increasingly higher affinity to an invading pathogen. This new finding from Whitehead Institute scientists overturns a previously held notion that only a narrow range of B cells can survive this training and go on to secrete high-affinity antibodies. This revised understanding may aid development of effective vaccines against HIV, influenza, and other viruses that mutate rapidly.
Whitehead Institute researchers have created a new mouse-human modeling system that could be used to study neural crest development as well as the modeling of a variety of neural crest related diseases, including such cancers as melanoma and neurofibromatosis. Mouse-human chimeras would fill an important gap in disease research, as existing models do not accurately mimic key disease processes, including solid tumor initiation and progression, and are of little value for studying diseases with long latencies, such as Alzheimer’s and Parkinson’s.
Whitehead Institute researchers have created a map of the DNA loops that comprise the three dimensional (3D) structure of the human genome and contribute to gene regulation in human embryonic stem cells. The location of genes and regulatory elements within this chromosomal framework will help scientists better navigate their genomic research, establishing relationships between mutations and disease development.
Whitehead Institute researchers have determined the organization of a protein complex that is critical during chromosome segregation. Without the foundation it supplies, the link between chromosome and kinetochore would fail, as would chromosome segregation and cell division.
Scientists at Whitehead Institute and Broad Institute of MIT and Harvard have for the first time identified the universe of genes in the human genome essential for the survival and proliferation of human cell lines or cultured human cells.Their findings and the materials they developed in conducting the research will not only serve as invaluable resources for the global research community but should also have application in the discovery of drug-targetable genetic vulnerabilities in a variety of human cancers.
Whitehead Institute scientists have at last answered the long-standing question of how the growth-regulating pathway known as mechanistic target of rapamycin complex 1 (mTORC1) detects the presence of the amino acid leucine—itself a key player in modulating muscle growth, appetite, and insulin secretion.
Whitehead Institute researchers have developed a tool that allows scientists to monitor changes in DNA methylation over time in individual cells. Certain diseases, including cancer, cause changes in DNA methylation patterns, and the ability to document these alterations could aid in the development of novel therapies.
A protein known to play a role in transporting the molecular contents of normal cells into and out of various intracellular compartments can also turn such cells cancerous by stimulating a key growth-control pathway.
In the breast, cancer stem cells and normal stem cells can arise from different cell types and tap into distinct yet related stem cell programs, according to Whitehead Institute researchers. The differences between these stem cell programs may be significant enough to be exploited by future therapeutics.
Upsetting the balance between protein synthesis, misfolding, and degradation drives cancer and neurodegeneration. Recent cancer treatments take advantage of this knowledge with a class of drugs that block protein degradation, known as proteasome inhibitors. Widespread resistance to these drugs limits their success, but Whitehead researchers have discovered a potential Achilles heel in resistance. With such understandings researchers may be able to target malignancy broadly, and more effectively.
By teasing apart the structure of an enzyme vital to the parasites that cause toxoplasmosis and malaria, Whitehead Institute scientists have identified a potentially ‘drugable’ target that could prevent parasites from entering and exiting host cells.
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