About Computational and Structural Biology in Biodefense
(CSBB)Training Program

Medical countermeasures to biological weapons and threatened newly emerging infections involve a combination of prevention through vaccination, rapid diagnosis, and treatment by novel drug development. Besides the dramatic new threat from bioterrorism, the past 20 years have seen a remarkable resurgence of infectious diseases and the emergence of new ones such as AIDS and SARS. One result of increased infectious disease burden is increased health care costs. The cost to our economy resulting from a larger bioterror attack is immense. Consequently, there is a critical need for scientists trained in structural and computational biology, genomics, proteomics and structure-based design of agents targeted to these diseases and threats to develop new therapeutics, vaccines and diagnostics.

The goal of the Computational and Structural Biology in Biodefense (CSBB) Training Program is to train first-rate, imaginative and creative scientists to become independent researchers in this multidisciplinary field of biodefense. Most importantly, the trainees selected for the program will learn the importance of cross-disciplinary research confronting problems in molecular medicine that are simply too complex to approach in the traditional, single principal investigator research mode. Solutions to such problems require the broad and extensive interactions and cooperative training that will be key aspects of this Training Program. The interdisciplinary, multi-institutional nature of the program, with an emphasis on biothreat countermeasures, will be a special attraction to top students in the nation.

The CSBB Training Faculty is a world-class group of

• virologists
• infectious disease researchers
• pathologists
• molecular biologists
• immunologists
• genomicists
• X-ray crystallographers
• NMR spectroscopists
• cryoEM microscopists
• computational biologists
• pharmacologists
• chemical biologists. 

These teams already often share laboratories, graduate students, post-doctoral fellows and staff to attack some of the most important issues facing defense against bioterrorism.

The CSBB Training Group has developed resources to

• understand the fundamental structural designs of the bioterror agents
• quickly identify and diagnose these new bioterrorism weapons
• sequence the entire genome of the viral pathogens and selected regions of bacterial genomes
• develop new vaccines
• identify potential drug targets through proteomics and genomics
• isolate and solve the 3D structure of pathogen proteins and entire viruses
• use rapid combinatorial, high-throughput screening and drug design methods to develop new drug leads against the infectious disease
• work with pre-established ties to biotechnology companies to test and deliver these drugs. 

The group is specifically developing a novel biodefense Training Program that will illustrate to trainees the interdisciplinary approaches required to develop new diagnostic tools, vaccines and drugs targeted to potential bioterrorist viruses, including alphavirues such as Venezuelan equine encephalitis, flaviviruses such as Langat and tick-borne encephalitis, and arenaviruses such as Pichinde and Lassa Fever, as well as other Class A, B and C pathogens such as anthrax.

The CSBB Training Program also benefits from state-of-the-art facilities.   In November, 2003,a Biosafety Level-4 * (BSL-4) laboratory, the BSL-4 Robert Shope Pavillion laboratory, was completed at The University of Texas Medical Branch at Galveston and is fully operational.  It is the only full-sized maximum containment laboratory located at a U. S. university and one of only 12 in the world. With this BSL-4 laboratory, CSBB trainees will have the ability to study many of the agents on the Centers for Disease Control and Prevention (CDC) and the NIH list of bioterrorism threats. In addition, the CSBB Training Program will utilize other facilities designed specifically for biodefense and infectious disease research at the six GCC institutions.

The GCC continues to act as a catalytic and facilitating organization to support the continued collaborative contributions of its member institutions and faculty at the most exciting frontiers for developing an understanding of basic biological processes including biodefense.

Training Faculty Research Interests in Biodefense

The major research topics in biodefense within our training faculty can be summarized using the NIAID list of priority pathogens according to the established A-C categories.  Note that the majority of these pathogens are being actively studied by our training faculty:

Category A

• Bacillus anthracis (anthrax): Terri Koehler, Ed Nikonowicz, Jim Briggs
• Francisella tularensis (tularemia): Gary Klimpel
• Viral hemorrhagic fevers:
• Arenaviruses (Lassa Fever, Junin, Machupo, Guanarito viruses): Norbert Herzog, C. J. Peters,
  David Gorenstein, Bruce A. Luxon, Robert Fox
• Bunyaviruses:
• Rift Valley Fever: C. J. Peters
• Flaviviruses:
• Dengue: Scott Weaver, Alan Barrett, David Gorenstein, Bruce A. Luxon, Norbert Herzog, Robert Fox, Hong Zhou
• Botulinum Toxins (Clostridiuim Botulinum):  Jim Briggs

Category B

• Typhus fever (Rickettsia prowazekii): David Walker
• Diarrheagenic Shigella species:
• Viruses (Caliciviruses, Hepatitis A): StanleyLemon, Mary Estes,
  B. V. V. Prasad, Robert Atmar
• Additional Viral Encephalitides:
  • West Nile Virus: Alan Barrett, David Gorenstein, Bruce A. Luxon, Norbert Herzog, Robert Fox, Kurt Krause, Hong Zhou
  • VEE Virus: Scott Weaver, Robert Davey, Stanley Watowich, David Gorenstein, Wah Chiu
  • EEE and WEE Virus: Scott Weaver
  • Japanese Encephalitis Virus: Alan Barrett, Robert Fox
  • Kyasanur Forest Virus: Alan Barrett
• Shigella Toxin:  Jim Briggs

Category C

• Tickborne Encephalitis Viruses: Alan Barrett, David Gorenstein
• Yellow fever: Alan Barrett, David Gorenstein, Robert Fox, Kurt Krause
• Influenza: Norbert Roberts
• Other Rickettsias: David Walker
• Other Flaviviruses: Hong Zhou
• MDR-tuberculosis: Kurt Krause

Another way of viewing the research capabilities of the participating training faculty is through the basic structural and computational biology studies relevant to biodefense and infectious diseases. Research areas include studies of:

• Protein-nucleic interactions (including VEE, WNV, arenaviruses, HIV-1, and other viral proteins)
  (R. Fox, Luxon, Gorenstein, Lee, Herzog, Weaver, Lemon, Peters, Nikonowicz, Gao, Chiu)
  
• Structure-based drug design and HTS of focused libraries
  (Pettitt, Fox, Luxon, Gorenstein, Davey, Watowich, Nikonowicz, Gao, Gilbertson, Krause, McMurray, Koehler, Peters, Briggs)
  
• Structural biology of viral infection
  (Pettitt, Chiu, Barrett, Zhou, Fox, Watowich, Gorenstein, Luxon, Herzog, Weaver, Davey, Lemon, Bourne, Peters, Krause, Lee, Estes, Prasad)
  
• Cellular response to infectious disease and signal transduction
  (Fox, Gorenstein, Luxon, Watowich, Bolen, Herzog, Weaver, Lemon, Roberts, Butel)
  
• Fundamental studies of macromolecular structure, stability and recognition; allosteric regulation
  (Chiu, Prasad, Zhou, Pettitt, Fox, Bolen, Lee, Gorenstein, Luxon, Krause, Hilser, Gao)
  
• Protein folding, genomics, proteomics, bioinformatics and systems biology
  (R. Fox, Chiu, Bolen, Lee, Luxon, Oberhauser, Gorenstein, Pettitt, Hilser, Palzkill, Weinstock, G. Fox, Watowich, Gao)
  
• Rational design of vaccines, viral structure and membrane proteins
  (Keitel, Barrett, Estes, Prasad, Gorenstein, Oberhauser, Chiu, Weaver, Watowich, Sastry, Ridge, Li, Spudich, Davey)

* BSL-4 laboratories are designed to prevent infectious microbes from being released into the environment and to provide the highest possible level of safety to scientists carrying out experiments with infectious microbes.