U.S. Department of Health and Human Services
Istvan Botos

 Contact Info

Tel: 301-443-3595
Email: botosi@mail.nih.gov

 Select Experience

  • Staff ScientistNIDDK, NIH2005–Present
  • Postdoctoral FellowFrederick Cancer Research and Development Center, NCI, NIH1999–2005
  • Research FellowHungarian Academy of Sciences, Institute of Biophysics1990–1992
  • Ph.D.Texas A&M University1999
  • M.Sc.University of Bucharest, Department of Biology1990

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Istvan Botos, Ph.D.

Staff Scientist, Office of the Chief, Laboratory of Molecular Biology
  • Structural Biology
Research Summary/In Plain Language

Research in Plain Language

Innate immunity is an organism’s first line of defense against invading infectious agents (pathogens). Without innate immunity, we would die from a simple bacterial infection. Our second line of defense, adaptive immunity, takes several days to respond. Innate immunity responds immediately when molecules from pathogens bind to particular proteins.

One family of proteins, toll-like receptors (TLRs), play an important role in the immune system. TLRs recognize a wide variety of molecular patterns associated with specific infectious agents. When TLRs detect these patterns, they trigger an inflammatory response to eliminate pathogens. These molecular patterns include ones associated with bacteria and viruses. To date, scientists have identified 12 types of TLRs in mice and 10 in humans. This raises the question: how can a few receptors recognize such a wide variety of molecules?

Our research group focuses on understanding TLRs. We primarily use X-ray crystallography, a method for studying molecular structure in detail. We also conduct biochemical studies. In 2005, we determined part of a particular TLR’s molecular structure in detail. This protein, TLR3, recognizes viruses by binding to their double-stranded RNA (dsRNA). We described particular parts of TLR3 that block binding of the dsRNA. We also investigated how the length of dsRNA affects binding to TLR3. We specified the minimum RNA length and identified protein to RNA ratios for binding. Using this information, we were able to describe how two TLR3 molecules work together to trigger a signal within the cell. The signal sets off a cascade of actions that leads to inflammation.