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Funding Opportunity
for Pilot & Feasibility Projects through the University of Chicago's
NIDDK/NIH-Sponsored Digestive Diseases Research Core Center (DDRCC)
SUBMISSION DEADLINE: SEPTEMBER 4TH, 2008
We are pleased
to announce the availability of funds for Pilot and Feasibility
Projects with a starting date of December 1, 2008.
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:
- Attracting
junior faculty members, including senior research fellows, into
the mission areas of 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 disease.
- Allowing
more established faculty members, who are not currently engaged
in gastrointestinal research, to extend their investigations into
mission areas of DDRCC.
- Permitting
any faculty member to test a novel hypothesis related to the mission areas of 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.
DDRCC
New Investigator: New investigators, defined as junior
faculty at the Instructor/Assistant Professor level, who do not
have NIH support and are in the formative stages of their career
development are also encouraged to apply for salary support by the
DDRCC. Compensation of up to 40% effort or a maximum of $40,000
for salary/benefits will be provided. Candidates must submit a P&F
application and provide a nominating letter from the Department
Chairman. Selection of the awardee will be determined by relevance of the proposal to the mission areas of the DDRCC, scientific
merit and novelty of the proposal and candidate's potential. Interested
candidates are encouraged to contact Drs. Jabri or Chang prior to submission
of their application for questions regarding eligibility and program relevance of their proposal.
Core
Laboratories:
- 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.
- Genetics/Molecular
Engineering Core (Director, Marc Bissonnette, M.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.
- 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.
- Systems
Biology Core (Director, Bana Jabri, Ph.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, 2007 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 (not P.I.'s salary), 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 Chang
prior to submitting a full application, ideally by August 10, 2007
(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 11pt. 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:
- Applications
will be initially reviewed by the Digestive Diseases Research
Core Center Executive Committee for their appropriateness for Pilot
& Feasibility funding.
[Application receipt deadline 9/4/08].
- Following
this initial review, applications may be returned for modification
prior to submission to the External Advisory Committee.
- 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 sometime in Oct-Nov 2008.
- Notification
of funding decisions will be made by the second week
of November.
- Funding
starts 12/1/08.
Funding
for Pilot and Feasibility Projects Application Format:
- Title of
proposal:
- Investigator(s)
and coinvestigators: (Name and academic title, e-mail address,
phone and FAX numbers)
- Specific
Aims:
- 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:
- Methods
of Procedure:
a. Subjects, animal model or in vitro system to be used
b. Experimental design
c. Laboratory methods
d. Analysis of data
- References:
- 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)
- Detailed
budget (for new submissions, indicate first year costs; for competing
renewals, indicate costs for a second year):
- IRB/ Animal
care review status and approval notification
- Biographical
sketch (NIH formatted)
- Other support
with dollar amounts listed.
PLEASE
DELIVER ORIGINAL PROPOSAL (ALONG WITH 8 COPIES) TO LYNN KACZMARZ,
ROOM BH M410 (4-5811).
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