NCRR 12-Month Research Training Program: Hypothesis Driven Research

Dr. Robert S. Bridges, Ph.D., Program Director

• Introduction
• Research Areas
• Administrative Structure
• Program Faculty
• Program Training
• Eligibility Criteria
• Stipends
• Application Procedures

Introduction

There is a need for veterinarians with research training to participate in academic as well as corporate based research in the fields of animal and human health. It is crucial for 21st century veterinarians to acquire the scientific skills and technical training together with the conceptual framework to participate both as independent researchers and collaborators to meet the projected research needs in biomedical sciences.

The objective of this training program is to provide bright, and highly-motivated veterinary students with a one year, in-depth research experience in a productive and active research setting that uses animal models to develop skills at hypothesis-based, biomedical research. The longer-term objective is to make this training experience a launching pad for career involvement in research for our veterinary students. Cummings School of Veterinary Medicine at Tufts University is addressing these objectives through the implementation of a new NIH training grant for veterinary students that will enable them to spend a year working intensively in a biomedical research laboratory.

Cummings School of Veterinary Medicine at Tufts University is making concerted efforts to strengthen its research/educational base. One mechanism that will contribute to our growing research and educational capabilities is a training program in biomedical research for our veterinary students. TCSVM presently has more than 20 research laboratories that are actively investigating animal and human-related health issues in the fields of infectious diseases, reproductive biology, biotechnology, hepatic function, neuroscience, nutrition, oncology, and respiratory physiology. Descriptions of these research areas with the faculty involved in the specific projects are provided below.

Research Areas

Biotechnology (Drs. Alcivar-Warren & Sarkar): This program combines molecular biological and genetic technology in basic and applied areas to investigate the control of aquatic animal health (shrimp) and the genetic engineering of various species, including horses, shrimp, and endangered species. Specific studies examine (a) genetic diversity in wild Penaeus monodon shrimp, (b) the regulation of mitochondrial DNA and genetic polymorphism in horses, and (c) the regulation of gene expression in muscle cells.

Digestive Diseases (Drs. Anwer & Webster): The overall emphasis of this program is to gain further insight into cellular and molecular mechanisms of hepatic and gastrointestinal diseases. Current studies include: (a) cellular mechanisms of programmed cell death in hepatocytes and in hormonal regulation of hepatic bile formation, (b) the regulation of hepatic bile acid transport by second messengers and protein kinases, and (c) the role of pH and calcium in bile acid-induced hepatotoxicity

Infectious Diseases (Drs. Donohue-Rolfe, Mukherjee, Tzipori & Widmer): This program supports, among other projects, two major multidisciplinary research initiatives: (a) Cryptosporidium parvum, one of the important opportunistic infections that complicates AIDS, and (b) E. Coli 0157:H7, a pathogen responsible for outbreaks of hemolytic uremic syndrome (HUS) in children and hemorrhagic colitis in children and adults. The C. parvum program includes studies on the molecular basis for attachment and invasion, cellular mechanism of disease including newborn calves, and immunological and host risk factors contributing to persistence of infection in the immunodeficient host. This research also involves the development of strategies for control of the disease in patients with AIDS, genetic finger-printing, and genetic methods of detection of C. parvum oocytes in waterborne outbreak of disease. Investigations on E. Coli include study of the molecular mechanism and pathogenesis of the disease, development of attenuated candidate vaccines for prevention of meat contamination, and pursuit of therapeutic reagents for prophylaxis for children. Other projects examine the transmission and biological basis of lyme disease.

Neuroscience and Behavior (Drs. Bridges, Byrnes & Mann): The major emphasis of this program is to understand the role of neurotransmitters, hormones and opiate peptides in maternal behavior, the secretion of pituitary hormones, and behavioral problems in animals. Research in Dr. Bridges laboratory focuses upon the physiological events underlying pregnancy and lactation that impact both behavioral as well as endocrine and neurochemical responses and functions in adulthood. In one project, studies are ongoing using the rat as an animal model to delineate the role of the neural prolactin-like system in both the onset of maternal behavior and in maternal memory. A long-term goal of this collaboration is to determine underlying biological processes associated with reproductive-related illnesses, such as postpartum depression and neglect. The second project (Dr. Mann's) examines the specific involvement of one area of the brain, the ventromedial hypothalamus, that is key to the establishment of maternal behavior. This project will help define neural pathways that underlie the regulation of maternal behavior. A third project (Bridges & Byrnes) examines developmental aspects of neuroendocrine functions in females. Using a combination of endocrine, neurochemical, and behavioral approaches, the effects of single and multiple pregnancies on brain dopamine functions are being investigated. The implications of these studies include both psychiatric, endocrine, and other health disorders. The final project (Dr. Byrnes) explores the effects of pubertal opiate addiction on subsequent endocrine and reproductive functions in female mammals.

Nutrition (Dr. Freeman): Dr. Freeman is a clinical researcher interested in the effects of nutrition on cardiac function and animal health (dogs and cats). Dr. Freeman has both a PhD in nutrition and a DVM from Tufts. Her studies focus upon nutritional modulation of cardiovascular diseases and nutritional support in critical care.

Oncology (Dr. Leav): This program includes studies ranging from the basic mechanism of oncogenesis to evaluation of various cancer treatment modalities. Currently, projects include the investigation of (a) the mechanism(s) of multi chemotherapeutic drug resistance, (b) genetic and protein markers for osteosarcoma and other tumors of bone and soft tissues, (c) the mechanism of hormonally-induced carcinogenesis of the rat prostate, and (d) evaluation of 9-aminocamptothecin for treatment of lymphosarcoma in dogs. Research efforts in this program are supported by grants form NIH and pharmaceutical companies.

Reproductive Biology (Drs. Ayres, & Bridges): This program combines developmental and molecular biological technology in basic and applied areas to investigate the physiological control of mammalian reproduction. Specific studies in this program include (a) the process of maturation of immature oocytes transferred to the pre-ovulatory follicle of the mare and the subsequent ability of these oocytes to be ovulates, fertilized and to develop into blastocysts, (b) mechanisms of early embryonic development in domestic (pig, cow) and laboratory animal (mouse, rabbit) models, (c) the production of transgenic laboratory and domesticated (e.g. caprine and porcine) species, to generate desired physical attributes, cell surface epitopes, secretory (milk) peptide production, and increased gonadotrophin production, (d) the role of hormones in maternal behavior, and (e) the effects of reproductive experience on neuroendocrine functions in female mammals (see Neuroscience area for greater description of these latter two projects). Other research in this group focuses on both fundamental studies of preimplantation stage embryos of domestic (goats, cattle, pigs) and laboratory animals (rodents), and applied studies regarding the reproductive efficiency in these species. With respect to the former, studies are ongoing on cell and molecular mechanisms that regulate early embryo development in pigs, cows, goats and rodents, including production of transgenic and cloned animals. Current research is directed at understanding cell cycle synchrony in cloned embryos produced by somatic cell nuclear transfer (NT) and in activation-induced interactions between nuclear and cytoplasmic factors associated with developmental competence of bovine, caprine and murine cloned embryos. Research efforts in reproductive biology are supported by grants from NIH, USDA, biotechnology companies and private foundations.

Respiratory Physiology (Dr. Hoffman): Dr. Hoffman is a DVM with research interests in respiratory physiology. Using the horse as an animal model, his research has focused upon animal models for asthma as well as normal respiratory function in the horse.

Administrative Structure

The program is by Dr. Robert Bridges, the program director, with the assistance of a program committee that includes two program members, Dr. Lisa Freeman, DVM/PhD - Assistant Professor of Clinical Sciences, and Dr. Arthur Donohue-Rolfe, PhD - Associate Professor of Biomedical Sciences. The committee coordinates all aspects of the program, including the recruitment of trainees, selection of trainees, overseeing the training program, and establishment of trainee research committees.

The program faculty presently is made up of 18 faculty members from each of three departments at TCSVM: Biomedical Sciences, Clinical Sciences, and Environmental and Population Health. The selection of program faculty is based upon (1) the track records of each faculty member in obtaining extramural research funding, and (2) their prior mentoring experience. Presently, 17 of the 18 faculty have active NIH or USDA funding, while 1 faculty member exclusively has corporate funding.

Program Faculty

Proposed Training

Advertising, Recruitment & Admissions:
All incoming as well as matriculated veterinary students will be contacted at the beginning of each academic year to invite applications to participate in the research program. First year students will have been told about the program during the admissions process to the veterinary school. Information about the program is incorporated as part of our admissions mailings to all applicants to the veterinary school. In addition, the program is advertised via notices to matriculated students over the internet as well as by posting hard copies of about the program on campus. First and second year students will have the program specifics presented during Dean's hour each fall.

The annual deadline for applications to the program is March 1st. See the admissions requirements for applicants. Applicants will have completed a minimum of one year of veterinary school prior to entrance into the program, but may not have graduated. Applications are reviewed by the Program Committee, and applicants notified of their acceptance by April 15th. Program participants will begin their traineeship on June 1st. Students can enter the program after their 1st, 2nd or 4th year of veterinary school.

Course Work and Training Opportunities:
The primary emphasis of this training program will focus on direct laboratory research experience. However, in addition to the involvement in laboratory research, students will take one mini-course during their training in the fall semester. This course entitled "The Fundamentals of Animal Research" will examine a combination of issues relevant to animal and laboratory research. These topics include (1) research ethics, (2) research methods and design, and (3) statistical analysis. The course will meet weekly for 2 hours and will be team-taught by program faculty. All trainees will participate in the weekly laboratory meetings of their mentors as well as attend the bimonthly seminar series offered by the Department of Biomedical Sciences. Upon completion of their traineeships, all students will present their research project and findings at the annual Student Research Day.

Recognition:
All trainees that complete the 12-month training will receive a Certificate at commencement that recognizes their participation in this program. This certificate will acknowledge their involvement in research in biomedical veterinary sciences and in this training program.

Eligibility Criteria

The eligibility criteria for potential trainees include the following:

1. Trainees should have successfully completed at least one year at TCSVM and are full-time students.
2. Trainees must be citizen or non-citizen nationals of the United States or have been lawfully admitted for permanent residency.
3. Trainees must be in good academic standing at TCSVM.
4. Minority students will be given strong considerations.

Stipends

Students accepted in the training program will receive a stipend equivalent to NIH guidelines for predoctoral fellows, approximately $16,000. In addition, funds are provided to pay for health insurance and to send each student to one national scientific meeting.

Application Procedures

The following documents are needed to complete an application for admission to the Master's program by the applicant.

1. Application form
2. Personal Statement from the applicant describing his/her interest in the program, prior experience in the field, and career goals.
3. Identification of a potential mentor, including a letter of interest submitted by the potential mentor.
4. Official undergraduate and graduate/professional transcripts.
5. GRE scores.
6. Two letters of evaluation from individuals with positions at academic institutions (at least one from a TCSVM faculty member).

The complete admission packet must be submitted to the Training Program Director by March 1st for consideration for admissions to the program. The Training Program Committee reviews the applications and will recommend their choices to the Dean. Admission decisions will be communicated no later than April 15th.