The human body is home to approximately 100 bacterial cells for every one human cell. Yet, remarkably little is known about the complex interplay that occurs daily between the genomes of bacteria living in the body and our own genome. Systems biologists have identified the field of host-pathogen interactions as one of the bold new frontiers for applying tools of genomics, proteomics, and bioinformatics towards the goals of elucidating communication between the genomes of microorganisms and mammalian genomes, in health and disease. This is the goal of investigators in the Sanford-Burnham Medical Research Institute's Inflammatory and Infectious Disease Center.
The need to understand and develop treatments for inflammatory and infectious diseases is very great. It is currently estimated that within the next ten years, many antibiotics currently employed for treating bacterial infections will no longer be effective due to microbial resistance. Drug-resistant strains of some pathogens, such as the bacteria that cause tuberculosis, have already appeared. Also, very few treatments for viral infections exist to date. Moreover, several deadly viral agents are on the rise, threatening increasingly larger numbers of persons worldwide. Recent world events have made clear the need for an understanding of the molecular mechanisms of disease in order to counter threats created by terrorists seeking to weaponize anthrax, ricin, smallpox, yersinia, SARS, and other biological agents against the United States.
A wide variety of chronic inflammatory diseases have been linked to dysfunctional host responses to pathogens, including rheumatoid arthritis, which affects more than 40 million Americans, inflammatory bowel diseases, affecting more than 55 million persons in this country alone, and multiple sclerosis, a progressive neurodegenerative disease. Researchers at the Sanford-Burnham Medical Research Institute are studying the cells responsible for inflammatory disease and recently discovered a human gene variant that prompts cells of the immune system to attack insulin-producing cells, causing type 1 diabetes. This gene variant also predisposes to rheumatoid arthiritis and other inflammatory diseases. These diseases are extremely debilitating and are becoming increasingly common in our aging population.
Study of infectious and inflammatory diseases is highly synergistic with the Sanford-Burnham Medical Research Institute's research strengths. The Institute has a strong presence in areas including: (a) cell adhesion, relevant to the mechanisms bacteria and viruses use to penetrate human cells; (b) apoptosis and cell death, processes that constitute part of the inflammatory response and are manipulated by pathogens to both kill and resist the immune system; (c) genomic instability, in which genetic changes result in the emergence of drug resistance; and d) carbohydrate structures as key recognition elements for inflammatory cells.
A central focus in the Inflammatory and Infectious Disease Center is the rational, structure-based design of small molecule inhibitors, using: crystallography and NMR to determine structures; and chemistry, high through-put screening, and in silico approaches to identify and test inhibitors. Sanford-Burnham scientists have a track record of success with these approaches. A team effort, published in the fall of 2001, determined the three-dimensional structure of the anthrax lethal factor, and based on this knowledge, two potential drug candidates are now under development to treat patients after anthrax infection.
Research in the Infectious and Inflammatory Disease Center is synergistic with work in the Sanford-Burnham Medical Research Institute's other major research centers, the Cancer Center and the Del E. Webb Neuroscience, Aging and Stem Cell Research Center. Microbial infections are linked to several cancers, and chronic inflammation is commonly associated with an increased risk of cancer; inflammation is also an exacerbating component of neurodegenerative diseases such as Alzheimer's.
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