The Genomic Revolution Implications for Treatment and Control of Infectious Disease: Working Group Summaries (2006) / Chapter Skim
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How Can We Use Natural Variation in Disease Resistance to Understand Host Pathogen Interactions and Devise New Therapies?
How Can We Use Natural Variation in Disease Resistance to Understand Host Pathogen Interactions and Devise New Therapies?
Pages 83-94
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From page 83... ...
Polymorphic susceptibility and/or resistance alleles at multiple genetic loci have been identified in human populations, as illustrated by the classic example of the sickle cell hemoglobin mutation, which confers resistance to malaria. The spectacular resources now available with the completion of the genome sequences for numerous mammalian hosts, as well as their specific pathogens, provide unprecedented opportunities to dissect these complex pathways of interaction and to identify new targets for therapeutic intervention.
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From page 84... ...
· As such specific resistance and susceptibility alleles are identified, often with widely different prevalences among human populations, what specific social or policy issues does this raise when approaching these populations? · What approaches should be taken to increase the interaction between infectious disease experts and geneticists in harvesting this enormous dataset?
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From page 85... ...
How can we use this natural variation to illuminate hostpathogen interactions and pave the way for new therapies? Asking these questions may seem silly when talking about the common cold, but when dealing with diseases such as malaria, TB, or HIV, it could mean life or death.
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From page 86... ...
The interdisciplinary studies would involve sequencing all host and pathogen genomes to identify the mechanisms of interaction and pinpoint therapeutic or vaccine targets. The ethical and legal issues would be staggering, but the group felt the potential benefits to society of controlling or eradicating deadly diseases would make the endeavor worthwhile.
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From page 87... ...
"In most medical schools, for example, there's a department of infectious disease and there are people who work in human genetics and they rarely talk to each other," the group spokesperson said at the final presentation. This has slowed progress in genomic research in regard to infectious disease, according to the group.
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From page 88... ...
These partnerships would be part of a broader infrastructure needed to appropriately integrate local data collection with large-scale genomic science. To carry out what the group called "big science," consortia would be needed involving partnerships between public and private institutions, to help address multiple diseases and to advance funding opportunities, and between scientists and legal professionals, to aid in obtaining informed consent and addressing privacy issues.
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From page 89... ...
In addition to the obvious benefits of improving health and economics, these studies would increase research and development capacity in developing countries by building facilities and forming partnerships between local scientists and large institutions. From a scientific standpoint, the group felt the project would increase basic understanding of how humans and pathogens interact, and provide a model for interdisciplinary science.
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From page 90... ...
90 THE GENOMIC REVOLUTION WORKING GROUP SUMMARY GROUP 2 Summary written by: Chandra Shekhar, Graduate Student, Science Writing, University of California, Santa Cruz Working group members: · Agnes Awomoyi, Microbiology and Immunology, University of Maryland, Baltimore · Phillip Berman, Scientific Director, Global Solutions for Infectious Diseases · Bruce Beutler, Professor, Department of Immunology, The Scripps Research Institute · Karen T Cuenco, Research Assistant Professor, School of Medicine, Boston University · Dennis Drayna, Chief, Section on Systems Biology of Communication Disorders, National Institute on Deafness and Other Communication Disorders, National Institutes of Health · Michael Fasullo, Senior Research Scientist, Cancer Research, Ordway Research Institute · Jonathan Kahn, Assistant Professor, School of Law, Hamline University · Rob Knight, Assistant Professor, Chemistry and Biochemistry, University of Colorado, Boulder · Erin McClelland, Research Fellow, Medicine, Albert Einstein College of Medicine · Bob Roehr, Freelance Science Writer · Michael Rose, Director, Intercampus Research Program on Experimental Evolution, University of California Systemwide · Chandra Shekhar, Graduate Student, Science Writing, University of California, Santa Cruz · Hongmin Sun, Life Sciences Institute, University of Michigan · Shan Wang, Associate Professor, Materials Science and Engineering, Stanford University
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From page 91... ...
In the midst of this intellectual sparring, some members felt we should not focus on one disease but on common disease pathways. The group finally hammered out a consensus: we would examine the effect of genomic variations on disease outcomes -- genotype-phenotype relationships -- for high-impact infectious diseases, including poorly understood ones.
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From page 92... ...
So one has to be cautious in applying insights from mouse models -- or from any other animal models -- to human diseases. Nonetheless, studying the effects of mutated mouse genes is a powerful technique for linking genetic variations to disease resistance.
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From page 93... ...
The first bridge addresses an evolutionary question: can we predict pathogen evolution as a function of host genome and environmental variations? Attempts to predict the evolution of influenza virus have already been published in the literature; our group was interested in seeing whether
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From page 94... ...
The progress of an infectious disease depends on how well the pathogen adapts to its environment. Our group proposed to track the ensemble of pathogen genomes as they adapt to the host under a range of environmental variations, including presence or absence of therapeutic intervention.
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