Funding Opportunity for
Pilot & Feasibility Projects through the University of Chicago's
NIDDK/NIH-Sponsored
Digestive Diseases Research Core Center (DDRCC)

We are pleased to announce the availability of funds for Pilot and Feasibility Projects with a starting date of December 1, 2009.

Purpose:

The overarching theme of the DDRCC is research in the areas of inflammatory bowel diseases (IBD) and intestinal inflammation, immunology, microbiology, and epithelial biology/cancer of the GI tract.  Pilot and Feasibility applications relating to these “mission” areas will receive higher priority.  Pilot and Feasibility awards are offered for the purposes of:

1.         Attracting junior faculty members, including senior research fellows, into the mission areas of the DDRCC. This is the principal target group and is intended ideally for candidates without current NIH or other significant extramural support to initiate research into digestive diseases.

2.         Allowing more established faculty members, who are not currently engaged in gastrointestinal research, to extend their investigations into the mission areas of the DDRCC.

3.         Permitting any faculty member to test a novel hypothesis related to any of the mission areas of the DDRCC, which might not yet meet NIH requirements of feasibility for R01 funding.

Applications which emphasize DDRCC core use and which will strengthen collaborative interactions among scientists within the digestive disease research community are particularly encouraged. It is strongly anticipated that the results of these pilot projects will eventually permit investigators to compete successfully for extramural research support in IBD and related areas of gastrointestinal research.

Research Topic:

Broad aspects of basic and translational/clinical research related to the microbiology, inflammation and immunology of the digestive tract and pathogenesis, genetics, pathophysiology, and bench-to-bedside applications of inflammatory bowel diseases will be given higher priority.  In addition, proposals focused on the examination of growth and differentiation, cancer biology, intestinal epithelial biology and pathobiology of the gastrointestinal tract (including the luminal GI tract, liver, pancreas, biliary system, etc.), as well as basic or clinical research in the areas of nutrition and digestive diseases are appropriate topics for Pilot & Feasibility studies.  Please feel free to ask for guidance if you are unsure about the suitability of your topic or project.

New Investigator Award
Funds are also available through the DDRCC for partial salary support of a New Investigator interested or engaged in research of digestive physiology and disease. Projects related to the “mission” area of the DDRCC (IBD and intestinal inflammation, immunology, microbiology, and epithelial biology/cancer) will be given higher priority.  These funds are available for a one or two year period to a junior faculty member (Instructor or Assistant Professor) in a clinical or basic science department.  The candidate must devote at least 40% effort to a Gastrointestinal-related project and must submit and be selected for a Pilot and Feasibility Award from the DDRCC (see Funding for Pilot and Feasibility Projects).
Nominations for this award must include:

• Current CV
• Nominating letter from the applicant's Department Chairperson.
• Brief description of the applicant's research program (two page maximum, single-spaced).
• A completed application (see Pilot and Feasibility Projects Application Format)

Core Laboratories:
1. Cell & Enteric Microbiology Core (Director, Eugene B. Chang, M.D.) - provides a large repository of transformed and non-transformed epithelial cell lines, specialized cell culture services (co-culture, organ culture, Transwell monolayers, and vector transfections).  In addition, we now offer core services in molecular–based approaches for the study of the enteric microbiome,.  Bioinformatic support is provided through the Systems Biology Core.

2. Genetics/Molecular Engineering Core (Director, Nathan Ellis, Ph.D., Co-director, David Boone, Ph.D.) - Real time PCR, DNA sequencing, genomic microarrays, proteomic analyses, DNA and RNA recombinant technologies.  New to the Core are the addition of services for creating somatic cell knock-ins or knock-outs and Bac clone recombineering for development of gene targeted deletion or knock-in constructs.

3. Tissue and Cell Analysis Core (Director, Jerrold Turner, M.D., Ph.D., Co-director. Vytas Bindokas, Ph.D.) – Service for analysis of human tissues and animal models of experimental intestinal inflammation including tissue processing and staining, use of cryostats and laser capture microdissection microscopes, access to confocal microscopes (IX81, SP2, SP5), and ACIS image analyzer use. Consultative services for tissue staining, morphological interpretation, and design of animal models of experimental intestinal inflammation are also available.

4.  Systems Biology Core(Director, Bana Jabri, Ph.D., Co-director, Marc Bissonnette, M.D.) - Consultative services for study designs (clinical studies, phenotypic and functional analysis of human blood and intestinal samples), IRB protocols, Human IBD registry and database, and human genetics of digestive diseases.

Past P&F Recipients:

By way of example, the range of research activities supported through this mechanism includes:

• Glenn Randall, Ph.D. (Department of Microbiology) “Identifying hepatocyte membrane trafficking pathways critical for Hepatitis C virus infection of the liver.”  Recently, hepatitis C virus (HCV) strains that are infectious in human hepatoma cells were identified. This provides the first opportunity to study how the virus enters and exits liver cells. We propose a combinatorial approach to dissect the roles of cellular membrane trafficking pathways in HCV infection. Our approach integrates RNA interference (RNAi) analysis, live cell microscopy, viral genetics, and biochemistry to probe viral trafficking in the infected cell.  This is likely to be especially fruitful, since HCV is thought to use membrane trafficking pathways at each step of its life cycle in a series of complex, overlapping interactions. An siRNA library was assembled that targets 136 genes likely to modulate viral infection, including all known pathways of receptor-mediated endocytosis (HCV entry), cellular membrane re-organization (HCV replication), and the secretory pathway (HCV exit). We have identified 44 host genes that are required for HCV infection. These cluster into specific pathways including clathrin-mediated endocytosis, actin/cytoskeletal re-organization, golgi structure and membrane re-organization, and components of the secretory pathway. We are currently assigning roles for these genes and pathways in viral infection using HCV cell culture systems that isolate specific stages of the viral life cycle.

• Kay Macleod. Ph.D. (The Ben May Department for Cancer Research “The role of autophagy and BNIP3 in preventing liver cancer progression.”  The goals of this project is to examine the role played by BNIP3 and autophagy in hepatocytes exposed to nutrient deprivation and oxidative stress. We are also aimed to determine whether BNIP3 plays a role in liver cancer progression. We are ascertained that BNIP3 is critical for hepatocyte mitochondrial integrity independent of exogenous stresses and that BNip3 null mice develop liver disease. Work is on-going to determine how BNIP3 affects predisposition to liver cancer.

• Mala Setty, M.D. (Department of Pediatrics): “Early innate immune events in the pathogenesis of celiac disease”  Celiac disease(CD), a genetic T cell (Th1) mediated inflammatory disorder induced by peptides of gluten, a wheat derived protein, recognized by MHC class II molecules DQ2 or DQ8 in the lamina propria (LP), leading to CD4+ T cell activation and IFN-g secretion. In addition, gluten peptides induces innate stress ligands on intestinal epithelial cell(IEC) recognized by natural killer receptors expressed by intraepithelial lymphocytes(IEL), leading to IEC destruction.  What remains unanswered is how, in celiac mucosa, are antigen presenting cells being activated to upregulate costimulatory molecules leading to a proinflammatory T cell response in the LP, and what are the events lead to arming IEL to kill distressed IECs.  We propose that IFN-a, shown to induce APC maturation and enhance effector cytolytic CD8+ T cell responses may play an important role in both these mechanisms.  We aim to understand this using multiple approaches to dissect the role of IFNa and it’s pathways in CD.  We have established the presence of significantly elevated serum IFNa expression among active CD patients using an interferon alpha ELISA (PBL Biomedical). In addition, using an antibody that recognizes MxA, an interferon-alpha inducible protein, we identified a significantly high expression of tissue MxA in intestinal biopsy section of active CD, both in the LP and the epithelium, as compared with controls, supporting the role of IFNa in CD mucosa.  With this preliminary data I was able to secure a competitive K12 grant (Research Career Training in Pediatrics).  Using APC cell lines we will dissect the pathway induced by specific gluten derived peptide sequences specifically looking at IFN—a transcripts and interferon inducible genes by RT-PCR, as well as IFN-a by ELISA.  Furthermore, signaling leading to IFN-a have been proposed through virally mediated pathways, which will be dissected using western blot assays on whole cell lysates of human APC and intestinal epithelial cell lines.  Confirmation of this pathway of activation will proceed by studying active CD patients through western blot of total lysates and flow cytometry. 

Period and Amount of Funding:

Funds for Pilot & Feasibility studies are available for an initial period of one year beginning December 1, 2009 and are limited to a maximum of $25,000 in direct costs. In general, funds have been allocated in the range of $15,000 to $20,000, although in exceptional circumstances, awards have been made up to the maximum allowable amount. Successful candidates are required to provide a progress report 6 months into the fiscal year for continuation of funding. Outcome of progress during the first year will determine if applicants will be invited to reapply for  a second year of funding.

Funds may be requested for personnel (PI salary not allowed – unless you are applying the New Investigator Award)), supplies, services and other costs (not equipment or travel). A detailed budget with justification is essential for the application.

Applications:

Interested applicants are strongly encouraged to contact Drs. Bana Jabri or Eugene B, Chang prior to submitting a full application, ideally by July 17, 2009 (i.e. 3 weeks prior to grant submission deadline).

Pilot & Feasibility applications should conform to a standardized format, which can be found below.   Science portion of grant should be no longer than 6 pages in length, 0.5 inch margins, minimum 11 pt. Arial.

Questions?

Bana Jabri, M.D., Ph.D. - bjabri@bsd.uchicago.edu (4-8670)
Eugene Chang, M.D. - echang@medicine.bsd.uchicago.edu  (2-6458)

Review and Processing:

1.         Applications will be initially reviewed by the Digestive Diseases Research Core Center Executive Committee for their appropriateness for Pilot & Feasibility funding.
[Application receipt deadline 8/7/09].

2.         Following this initial review, applications may be returned for modification prior to submission to the External Advisory Committee.

3.         The completed applications will be reviewed by members of the External Advisory Committee of the Center with respect to their scientific merit, etc. Funding priorities will be determined by the DDRCC External Advisory Committee which will meet in mid-September, 2009.

4.         Notifications of funding decision will be made by the second week of November.

5.         Funding starts 12/1/09.

Funding for Pilot and Feasibility Projects Application Format:

1.         Title of proposal:

2.         Investigator(s) and Co-Investigators: (Name and academic title, e-mail address, phone and FAX numbers)

3.         Specific Aims*:

4.         Significance/Project narrative (6 page limit, minimum 0.5 inch margins, 11 pt. Arial)*:
a. Background and rationale for proposal:
b. Preliminary observations, if any:
c. Relation to longer term objectives and potential funding sources:

5.         Methods of Procedure*:
            a.         Subjects, animal model or in vitro system to be used
            b.         Experimental design
            c.         Laboratory methods
            d.         Analysis of data

6.         References:

7.         Justification and Need for Center Use of Funding:
(Pilot & Feasibility projects may contain request for Center core laboratory use in addition to other costs)
a. Narrative (5-10 lines): describe why the Center is needed and which Center core laboratories are involved (if any)
b. Amount of Center use if applicable (i.e. how many tests are to be done, over what time period will study be performed)

8.         Detailed budget (for new submissions, indicate first year costs; for competing renewals, indicate costs for a second year):

9.         IRB/Animal care review status and approval notification

10.       Biographical sketch (NIH formatted)

11.       Other support with dollar amounts listed.

PLEASE SEND TOTAL APPLICATION IN PDF OR WORD FORMAT (one document) TO FRAN VUKOVICH NO LATER THAN AUGUST 7, 2009 5:00 PM
(email: fjackson@medicine.bad.uchicago.edu)