Computational and Structural Biology in Biodefense
Training Program Curriculum

Our Vision

We envision a new generation of bioscientists who have a deep understanding of the biology and medical consequences of bioterror agents and the technical capability of handling these agents and characterizing their molecular structures with the eventual goals of developing new vaccines and therapeutics. We recognize that many of these agents present technical challenges for structural studies such as structural flexibility of the molecular components and currently limited availability of highly purified materials. Our trainees will engage in a new territory of research which is more demanding than conventional and currently available technologies. Our training faculty are committed to make a collective effort in meeting this challenge.

The six GCC partner institutions provide a uniquely rich teaching environment, including a diverse set of courses in biological sciences, biodefense, infectious diseases, and structural and computational biology that are directly appropriate for this program. In addition to taking formal courses related to their graduate degree, all trainees must take the Foundations course -- “Biothreat Agents and Biodefense” -- and participate in several cross-training seminar series. Trainees also will present their work at least once a year in student seminars, programs, or research conferences and are required to attend the Keck Annual Research Conference and the Annual Structural Biology Symposium.

Although the curriculum below refers only to courses offered at UTMB, it is possible to fulfill all curriculum requirements either in Galveston at UTMB, or in Houston at Baylor College of Medicine and/or UT Health Science Center at Houston.

Foundations – required of all trainees

•   Biothreat Agents and Biodefense course
•   Structural and Computational Biology in Biodefense Seminar Series
     This series creates a networking opportunity for the trainees and faculty in the CSBBTraining Program. These seminars will be held twice-monthly at UTMB and teleconferenced to the other GCC/Keck institutions.  Trainees are encouraged to remain after the seminars to discuss scientific issues with the speaker and with each other.
• Colloquium of Frontiers in Infectious Disease and Tropical Medicine
  This seminar series, held weekly at UTMB (PATH 6254), cross-trains students in the frontiers of infectious diseases and tropical medicine as well as biodefense. Local and visiting scientists are invited to present their most recent research in the fields ofinfectious disease, tropical medicine and biodefense.
• Keck Center Seminar Series
  Held weekly at Rice University and teleconferenced to UTMB, these seminars offer presentations by renowned local and national bioscientists. Trainees and faculty from the eight Keck Center training programs attend, and there is informal discussion and networking afterwards.
• 2-3 Research Rotations*
         *Research rotations are treated as courses at most of the GCC institutions. They are variable in duration (8 or 16 weeks) and credit hours depending on the graduate program.

Specific Trainee Course Requirements  for Computational and Structural Biology in Biodefense (CSBB)

The specific curriculum required for CSBB predoctoral trainees is carefully crafted to suit his/her specific needs based on his/her transcript of previous studies, prior field(s) of study, research interests, and long-term career goals. While this approach takes considerably more time to administer and implement than a fixed curriculum, the result is a trainee with the balance of exposure required for effective cross-training. Our strict requirement is that trainees entering the program MUST take, for credit, three courses in their discipline's complementary area, in addition to the five Foundations requirements described above. Given that six institutions are involved, the array of possible courses to meet these requirements is impressive. Additional biodefense courses that involve Keck faculty will be developed in the future.

Our goal is to cross-train students with a primary and secondary mentor in our two targeted fields of biodefense.  Consequently,

• students in biosciences/infectious diseases must take three mathematics, structural and computational biology, and/or computer science courses relevant to their interests;
• students in structural and computational biology, computer science or mathematics must take three biosciences/infectious diseases courses relevant to their background and research interests;
• students in physics, chemistry, or engineering backgrounds, may be required to take additional courses in both areas to reach the desired level of competence.

Electives: Selection of electives will depend, in part, on the core course requirements of individual graduate programs, but trainees are expected to do a minimum of 6 electives (3 from List A, and 3 from List B). The following list of electives is available:

List A. Biodefense/Infectious Diseases

List B. Computational/Structural Biology

Because the specific curricula vary substantially, two prototypic examples are provided:   one for a trainee with an infectious disease/biodefense background; the other for an individual with a structural/computational biology background.  The trainees will have the opportunity to select different career tracks.

Example:  Course requirements/electives for Trainees with Biodefense/Infectious Diseases Backgrounds

Interest: Molecular mechanisms and biodefense of pathogenesis   
List A electives: 2, 3, 15
List B electives: 1, 2 5

Interest: Molecular and structural biology of BWT agents                
List A electives: 7, 8, 9,15                                                                                                        
List B electives: 1, 2, 8  

Interest: Molecular immunology and biodefense                              
List A electives: 10,11,12,15                                                                                                      
List B electives: 1, 2, 7

Example: Course requirements for Trainees with Structural and Computational Biology Backgrounds

Interest: NMR Spectroscopy and biodefense                                   
List A electives: 2, 3, 15                                                                                                           
List B electives: 1, 2, 5

Interest: Molecular and structural biology of BWT                           
List A electives: 2, 8, 9       
List B electives: 2, 8, 10

Interest: CryoEM of BSL-3/4-level pathogens and biodefense          
List A electives: 2, 3, 8                                                                                                             
List B electives: 2, 5, 8                                                                                                      
Training in high containment laboratories (see below).

Interest: Bioinformatics and genomics in biodefense                       
List A electives: 2, 7, 15     
List B electives: 8, 12,17

Interest: Structure-based drug design and biodefense                     
List A electives: 2, 4, 15
List B electives: 8, 15, 18

High Containment Laboratory Training

Trainees whose research projects require high containment work will receive appropriate training at their institution (for BSL-3) or at UTMB (for BSL-4) laboratory training. This will provide training for students to carry out cryoEM, multi-photon microscopy, animal MRI in unique BSL-3 (and later in the Galveston National Laboratory) and BSL-4 environments. Training will also be offered to CSBB trainees at GCC/Keck institutions whose research does not require this containment level but who desire this experience to augment their overall experience and future career. The Office of Health and Safety Services also participates in these training activities, which are overseen by the campuses’ Biological Safety Committee.

Additional Requirements

Predoctoral students must also meet the requirements of their home departments, including rotations that can occur at any of the institutions.  This base ensures a traditional disciplinary background for future career opportunities.  Requirements of the home departments include coursework, oral and/or written candidacy exams, grade performance standards, research progress reviews, thesis defense and publication, and other department-specific requirements.

Faculty mentors must be from the list of Keck Center faculty.  Dual mentorship (one in biomedical/biodefense science and one in structural/computational science) is required. It is also expected that trainees will perform research in the secondary mentors laboratory as part of a “sabbatical.”

This curriculum will educate the trainees in the broad interdisciplinary field of biodefense covered by the CSBB Training Program. Thus topics treated in the course program will include;

• structural biology (protein structure determination through X-ray diffraction, cryoEM and NMR spectroscopy),
• protein and nucleic acid biochemistry and biophysics,
• modern biotechnology methods including genomics,
• proteomics and bioinformatics,
• protein engineering,
• computational and modeling methods,
• pharmacoinformatics,
• drug design,
• pathophysiology,
• molecular genetics of viruses,
• prokaryotic and eukaroytic systems,
• host-parasite relationships,
• signaling pathways
• pathogenesis of infectious diseases.

A multidisciplinary approach is requisite to achieving the level of understanding necessary for training in the biodefense field. We believe that the structural biologist of the future must be prepared to use, directly and not just by collaboration, all aspects of modern biotechnology and must be capable of developing a depth and breadth of understanding in an important biomedical field such as infectious diseases, and must be trained, if appropriate, to work in a BSL-3/-4 laboratory. Similarly a new breed of infectious disease scientists and researchers must be capable of utilizing the fields of structural biology, structural/functional genomics, proteomics, systems biology, and bioinformatics and be able to utilize advanced imaging instrumentation. This future hybrid scientist must further be able to assimilate new knowledge which will be generated at a breathtaking pace in the coming decade, and continually develop new skills and collaborations in order to remain productive and competitive.

Yearly Description of the Training Program 

Year 1. Students are supported in the first year by their respective Graduate School. There are two paths for admission to the Training Program. One assumes that students begin participation in the cross-training Program in their first year, although unfunded. We appreciate however that many very well qualified students might start their academic career in either ID/biodefense or computational/structural biology and then in the second year consider applying for our cross-training program. We will permit both options. For those students who consider the cross-training program in the first year, the Biodefense Program Recruitment and Admissions Committee will host information sessions for students interested in biodefense, where students will meet Training Program faculty and learn about their research. First-year students will also benefit from the program through systematic contact and advice from members of the Admissions and Recruitment Committee, assignment of a temporary advisor pending selection of a major professor, and participation in the Computational and Structural Biology in Biodefense seminars,   the Frontiers in Infectious Disease and Tropical Medicine seminars, and Keck Seminar series. Each graduate program and the Multidisciplinary Infectious Disease Research Program has weekly "work-in-progress" seminars and journal clubs for trainees to attend and keep abreast of current developments in their fields. Schedules for these events are published in a weekly calendar and monthly planner available to all trainees and distributed electronically through the Keck Center. In each of the first three years of training, each trainee is expected to attend a minimum of one "work-in-progress" seminar each week. Following the seminar, trainees will write a one-page critique to the Seminar Committee to demonstrate understanding of the seminar topic and to evaluate the strengths and weaknesses of the presentation.

They will benefit from the program by systematic contact and advice from members of the Admissions Committee and Keck faculty (who will also recommend course programs), assignment of a temporary advisor pending selection of co-mentors, participation in the weekly and monthly seminars, and by participation in the annual Structural Biology Symposium, Keck Annual Research Conference, and Biodefense/Keck/Frontiers seminars. A major part of the first year will be directed towards training in core courses in biochemistry, genetics, microbiology, structural biology, pathology and infectious diseases. Students will be housed in the research space of the temporary advisor. In the first year of pre-doctoral training, each trainee is expected to attend one graduate student seminar each week. Each trainee will present at least one seminar in this program a year. They will participate in all training group seminars, retreats and programs, just as the second and later year trainees, to ensure their unique identification with the Program.

In the second semester of the first year, students will again meet with the Admissions Committee for review of their training program course work and begin research rotations (10-15 weeks), providing students with ample opportunity to become acquainted with the research foci of multiple faculty members. Before the start of laboratory rotations, each graduate program hosts an orientation and poster session with the first-year students to introduce them to labs and research opportunities. The sessions are attended by faculty and graduate students in the respective program to assist first-year students in their program decision.  To ensure appropriate matching of trainee and co-mentors, a rotation must be accomplished in each of their laboratories, and cross-training will be emphasized. Also, all trainees at our institutions will take their comprehensive exam by the end of their first year. (If this is not possible, some students may delay entry into the Training Program until the middle or end of the second year.) At the end of year one, trainees who have performed well and are retained in the CSBB Training Program will receive training grant support in their second year. During the first two terms and summer, each student at our institutions is required to gain exposure to the research being undertaken at their institution through rotations. By the end of year 1, students select their graduate program and, in most cases, their primary and secondary co-mentors. The goal of the rotations is to allow students to experience the research environments and approaches in several labs and to interact with several potential mentors before committing to a particular laboratory for their dissertation research. Faculty also evaluate the potential of each student and his/her ability to adapt to a particular research environment

Year 2. Students will be required to choose both co-mentors at the beginning of their second year, when funding by their Traineeship normally begins. An alternate entry point is also possible for potential trainees who have not worked with the Admissions Committee starting from their first year. For these students, they must begin their coursework in the training program and participate in the seminars after they have been offered a Traineeship. For both paths, trainees will continue to complete the required Foundation as well as appropriate cross-training electives in the Training Program. Students will continue to participate regularly in the seminar series and attend the yearly research conference, regional and national meetings. Trainees will be encouraged to attend at least one technical meeting during their Traineeship period at Training Program expense. In their first and second years, they will be directed to summer schools or Gordon Conferences appropriate to their interests. All trainees will be evaluated at the end of each term by the Admissions Committee and the Training Directors. Each trainee will be expected to give a seminar on their research sometime during year 2.

Students begin to further develop their dissertation projects during the early part of year 2 (their projects and their presentation to the Training Directors is an important part of the evaluation process for selection). Also, all graduate programs have requirements for teaching and grant proposal writing in the second year. Students continue in the collaborating graduate programs to complete specific graduate program requirements, and concomitantly enroll in biodefense core requirements either as part of their primary discipline or as required electives of the particular graduate program.  Program students will continue to participate regularly in the Computational and Structural Biology in Biodefense, Keck Seminars and the Frontiers in Infectious Disease and Tropical Medicine seminar series. Support during this period will generally be from the training grant; however, students will not receive support until they have completed their qualifying exams for doctoral candidacy, which may defer program funding until the end of the first or second semester of the second year for some students.

Year 3.  Students will continue in their Traineeship with their approved dissertation work and complete any additional course work desired or suggested by the dissertation and Admissions Committees. As a means to mark their accomplishment in their research work, these senior trainees will give posters at the Keck Annual Research Conference. Regular participation in the three Foundation seminar series will be required, and attendance and presentations at regional and national meetings are expected. Primary direction and day-to-day advice and evaluation will be obtained from the co-mentors and the dissertation committee, which must include at least one member of the Keck faculty, in addition to the co-mentors. To remain on Traineeship status, students must maintain outstanding progress. The Recruitment and Admissions Committee will monitor the progress of each trainee on an on-going basis and provide written evaluations at the end of each semester.

Year 4 though graduation. We hope to ensure that these students remain a distinctive group throughout their graduate careers to emphasize the special, multidisciplinary nature of this program. To this end, trainees will continue to attend all functions of the Keck Training group, including the Keck Annual Research Conference. The students will be supported by grant funds from their co-mentors. This policy enables the CSBBTraining Program to be maximally cost-effective. Students will continue to be identified as part of the Keck Training Program, while a Training Program stipend is used for additional students. It is estimated that most Trainees will complete the requirements for the Ph.D. by the end of their fourth or fifth year. At any point during the training period, students not exhibiting the highest academic standards or failing to progress adequately towards their degree objectives will be subject to removal from the Training Program.