NIH Director’s Lecture
As part of NIH’s Wednesday Afternoon Lecture Series, the Director’s Lectures feature leading researchers from around the globe. Nominated by scientists and interest groups throughout NIH, the NIH Director specifically approves these annual lectures. There are approximately three NIH Director’s Lectures per year.
Dysregulation of the immune system and host-microbiota interaction has been associated with the development of a variety of inflammatory as well as metabolic diseases such as obesity and diabetes. Recent studies in Dr. Flavell's laboratory have elucidated the important function of inflammasomes as steady-state sensors and regulators of the gut microbiota. Mice with a disrupted inflammasome pathway have been shown to develop a colitogenic microbial community, which results in exacerbation of chemical-induced colitis and diet-induced steatohepatitis, obesity and type 2 diabetes.
A search for the origin of our adaptive immune system has revealed that the jawed vertebrates and jawless vertebrates (lampreys and hagfish) use different strategies for generating large repertoires of lymphocyte receptors for antigens.
Typically, the genetic cause of a disease is identified by studying the DNA of affected individuals, finding the responsible gene, and trying to understand how a mutated version might have coded for a defective protein that led to the disease. Dr. Fuchs, however, has pioneered “reverse genetics”: She starts with the protein abnormality and works backwards to identify the human disease. She has applied this strategy to elucidate the genetic basis of a number of blistering skin disorders and tumors.
Dr. Saphire’s lab studies viruses with compact genomes that encode just four to seven genes each. Viruses with limited genomes offer a defined landscape of possible protein-protein interactions. Each protein is critical—many are obligated to perform multiple functions and some rearrange their structures to achieve those new functions. As a result, these few polypeptides accomplish a surprisingly complex set of biological functions including immune evasion, receptor recognition, cell entry, transcription, translation, assembly and exit. Dr.
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