NIH Funds Research on New Antibiotics TROPHY Trial Update Research Dilemmas Recent Grant Proposals Submitted to External Agencies
	If at First You Don't Succeed....Figure Out Why

Jack Blazyk, Ph.D., Professor of Biochemistry in the Department of Biomedical Sciences and Associate Dean for Research, recently received a two-year Academic Research Enhancement Award for $145,000 from the National Institutes of Health to support his ongoing research on antimicrobial peptides.

Since World War II, antibiotics have proven very effective in eliminating or at least greatly reducing the incidence of many diseases caused by bacteria because these compounds possess the necessary selectivity to attack bacterial cells while sparing human cells. Unfortunately, the widespread use of common antibiotics such as penicillin has selected for resistant strains that are no longer susceptible to these agents. Since resistance is appearing to even the most potent antibiotics, such as vancomycin, the development of new approaches in antimicrobial therapy is imperative.

The discovery of naturally occurring antimicrobial peptides opened a new dimension for antibiotic development. Magainins, isolated from frog skin, are representative of the class of small linear cationic peptides that can kill both Gram-positive and Gram-negative bacteria by increasing the permeability of the plasma membrane at concentrations that do not induce hemolysis (i.e., they do not harm red blood cells). PGLa, also isolated from frog skin, has greater antimicrobial activity than magainins while retaining low toxicity to human cells. Blazyk is attempting to use these natural peptides as models to develop more potent and selective analogs that can be used therapeutically to treat bacterial infections.

Magainins and PGLa form a structure called an alpha-helix when they bind to bacterial membranes. It was believed that the alpha-helix structure was essential for antimicrobial activity. Blazyk found that linear peptides forming a beta-sheet structure could have equivalent antimicrobial activity and better selectivity between bacterial and human cells. In February, Ohio University filed a provisional patent application for this new class of beta-sheet-forming peptides.

Three graduate students (Yi Jin, Yu Zhang, and Fang Zhu), a lab technician (Janet Hammer), and numerous undergraduates are working on this project. Many new compounds will be synthesized and tested. The results from this work should facilitate the design of effective antimicrobial peptides that will augment the arsenal of available antibiotics in order to keep pace with the ever increasing resistance of bacteria to the drugs in current use.

The recruitment period in the TROPHY (Treatment of Preventing Hypertension) trial is approaching the end of the first year, and OU-COM is being commended as one of the nation's leading centers. TROPHY will determine whether blocking the action of Angiotensin II at the AT1 receptor can prevent the progression of high-normal blood pressure to clinical hypertension. In a recent letter from Shawna Nesbitt MD, National TROPHY Coordinator, OU-COM was recognized as #4 out of 92 national clinical centers participating in the trial.

In addition, the IBAH US Clinical Quality Assurance team recently visited OU-COM's clinical drug trials unit and two other leading TROPHY centers. The primary purpose of their visit was to assess techniques that could be generalized for use at other centers. Following the visit, the team commended the OU-COM center for excellent performance.

Questions regarding the TROPHY trial can be directed to Jack Brose, DO (principal investigator), Lori Arnott, RN (study coordinator), or Rosemary Vance, LPN (study nurse). Co-investigators in the TROPHY trial are Christopher Simpson, DO, Jim Sammons, DO, Jay Shubrook, DO, and Bob Gotfried, DO.

Q: Do Case Presentations Require Institutional Review Board (IRB) Approval?

A: Recently representatives of the Ohio University IRB and the Ohio University Office of Research & Grants and Sponsored Programs (ORSP) reviewed this issue. Whether a case presentation requires IRB review depends on the intent or outcome of the case study. If the presentation of the case study is for educational purposes (to prove that a student can present a case or to relay clinical information about a patient), then it doesn't qualify as research, and therefore does not require IRB review. If the presentation is to provide generalizable knowledge, i.e. a presentation at a conference or a publication in a journal, then it is research and does require IRB review.

Q: Does the IRB require consent forms for survey research?

A: According to Beckie Cale, Compliance Manager for the Ohio University IRB, some form of consent is required for almost every survey, thought it doesn't always have to be signed. Sometimes it is in the form of a cover letter with the survey. It includes at a minimum:

• Description of research
• Benefits
• Risks
• Confidentiality
• Voluntary participation

If you have questions about these or other research issues, you can contact Judi Rioch, Research Office Administrative Assistant (740 593-2336) or Jack Brose, DO, OU-COM Assistant Dean for Clinical Research (740 593-2247).

Recent Grant Proposals Submitted to External Agencies

PI: Rebecca Code, Ph.D.
Agency: NIH
Title: Opiod receptors in chick cochlear nucleus
Amount: $145,000 (FUNDED!)

PI: Mario Grijalva, Ph.D.
Agency: American Heart Association
Title: Host factors involved in parasite tissue tropism and cardiac pathology seen in experimental Tryparosoma
Amount: $260,000

PI: Mario Grijalva, Ph.D.
Agency: American Red Cross-Central Ohio Region
Title: Seroprevalence of Chagas disease in the blood banks of Ecuador
Amount: $3,000

PI: Peter Johnson, Ph.D.
Agency: NIH
Title: Fetal ethanol exposure and cellular changes in rats
Amount: $145,000

PI: John Kopchick, Ph.D.
Agency: COBASE-National Research Council
Title: Biochemical role of reactive oxygen species in senescence process
Amount: $8,099

PI: Alfred Pheley, Ph.D.
Agency: Agency for Healthcare Research and Quality
Title: Planning a research network in Appalachian Ohio
Amount: $101,908

If at First You Don't Succeed....Figure Out Why

by Al Pheley

Most of us have had our share of rejection - from applications to medical school, to scholarship applications, to love. Applying for research funding is no different. When seeking external grant dollars, almost every funder receives more applications than they can possibly support. And although you may believe your project is the best, review committees must make some choices. In a chapter of the Ohio Grants Guide, Richard Male has identified the 10 most common reasons that grants are declined. They include:

1. "The organization does not meet our priorities." Find out if the funder supports your type of research AND your type of institution (e.g., non-profit vs. for-profit).
2. "The organization is not located in our geographic area of funding." Many corporate funders only support projects in areas in which their employees live.
3. "The proposal does not follow our prescribed format." Follow their instructions to the letter. Do not go over page limits, make sure the type font and margins are correct, and include all of the requested information.
4. "The proposal is poorly written and difficult to read." After the first two drafts of a proposal we become too familiar with it. Have fresh eyes read it and give feedback. Avoid jargon.
5. "The proposed budget and grant request is not within our funding range." If the funding line is unclear, call the contact person. Submit realistic budgets.
6. "We don't know these people - are they credible?" Especially true with foundations - try and meet with the foundation staff before submitting the proposal. Let them get to know you. If you are new to the field, use consultants to establish credibility.
7. "The proposal doesn't seem urgent - and I am not sure it will have an impact." Include a well- justified problem statement and explain why now is a good time to address the problem.
8. "The objectives and plan of action of the project greatly exceed the budget and timelines for implementation." Plan a realistic effort. Practice the KIS method - keep it simple.
9. "We've allocated all the money for this grant cycle." There is only so much money to go around. Reapply during the next cycle. In the meantime, make sure the funder has a chance to get to know you and discuss your project with them.
10. "There is insufficient evidence that the program will become self-sufficient and sustain itself after the grant is completed." While oriented towards service grants, this comment shows the importance of demonstrating that the project you are developing will have long standing benefits.

Contact Judi Rioch at 740-593-2336 or rioch@ohiou.edu for details

Research Project Grants (R01)
Research project grants are awarded to institutions on behalf of a principal investigator to facilitate pursuit of a scientific focus or objective in the area of the investigator's interest and competence. Institutional sponsorship assures the NIH that the institution will provide facilities necessary to accomplish the research and will be accountable for the grant funds. Applications are accepted for health-related research and development in all areas within the scope of NIH's mission.
Deadline: October 1, 2000
Award: July 1, 2000
Amount: Up to $500,000 direct costs per year for up to 5 years

AREA -- Academic Research Enhancement Award (R15)
The Academic Research Enhancement Award (AREA) is designed to enhance the research environment of educational institutions that have not been traditional recipients of NIH research funds. This award provides limited funds for faculty members of these institutions to develop new research projects or expand ongoing research activities in areas related to the health sciences and to encourage students to participate in the research activity.
Deadline: September 25, 2000
Award: July 1, 2001
Amount: Up to $100,000 total direct costs over 1 to 3 years

National Science Foundation Regional Grants Conference

October 11-13, 2000
Purdue University
West Lafayette, IN

The conference includes sessions covering all aspects of the NSF proposal and awards process, including proposal and merit review, introduction to FastLane, award and administration, challenges, opportunities and new directions, and breakout sessions by discipline. For more information contact the NSF policy office at703-306-1243 or by email at policy@nsf.gov.