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Research Services
presents
Study Section Trends:
Re-submissions
Emcee: Toni D’Agostino,
Director, Office of Sponsored Programs
Study Section Trends
• Agenda
– Welcome, Announcements and Introductions
– Panelists’ Presentations
– Discussion
Study Section Trends
• Moderator
Miles Cloyd, Ph.D.
• Professor, Microbiology & Immunology
• Panelists
Tracy Toliver-Kinsky, Ph.D.
• Associate Professor, Anesthesiology
Satish Srivastava, Ph.D.
• Professor, Biochemistry & Molecular Biology
Grant Resubmissions:
Approach to critiques and revisions
Tracy Toliver-Kinsky, PhD
Associate Professor
Anesthesiology
Grant Resubmissions:
Approach to critiques and revisions
• Call your program director
• Response to reviewers
• Revisions
Grant Resubmissions:
Approach to critiques and revisions
Points to remember:
• You have only two more chances to get the
application funded
•“Burden of proof” is on you
• Things that may seem obvious to you may not
be to the reviewer
• Application may be read quickly and only once,
so your writing must be unambiguous
• You do not want to offend your reviewers, even
if they are wrong
Grant Resubmissions:
Approach to critiques and revisions
Step #1: Call your program director
Response to reviewers
• Brief introduction
• thank the reviewers for their suggestions
• brief summary of revisions (if possible)
• indicate how changes are marked in
application
• Respond directly to every concern the
reviewers raised
• Tip: paste every concern, number
them, then respond point-by-point
Response to reviewers
•Brief introduction
• thank the reviewers for their suggestions,
• brief summary of revisions (if possible)
• statement of how changes are marked in
application
Example:
“Introduction to Revised Application
We would like to thank the reviewers for their enthusiasm regarding this
project, their thoughtful criticisms, and for the useful suggestions. Reviewer #1 was
concerned with the design of the immunization schedule in aim 1, the time frame of
cytokine assessments in aim 2, and the ability to successfully perform adoptive transfer
of immune cells in aim 3. Reviewer #2 was predominantly concerned with the
characterization of dendritic cells before and after treatment, and with potentially
adverse/systemic side effects of Flt3L treatments. We have responded to all concerns
in a point-by-point reply and have revised the application accordingly. Changes to
the original application are marked by a vertical line in the left margin.”
Response to reviewers
Respond directly to every concern the reviewer raised: describe revisions
Tip: paste every concern, number them, then respond point-by-point
Reviewer 1
1) “There is some concern about the way these immunization studies are designed. The mice will
be immunized 1 week prior to injury, then boosted with TT at 13 days after injury. This approach
will indicate how injury influences an ongoing T-cell response rather than a response that will be
influenced by the injury or FLT3L treatment.” We would like to thank the reviewer for
recognizing the flaw in the previous immunization schedule. We have redesigned this
experiment with two different immunization protocols that will permit dissection of the effects of
injury and Flt3L treatments on both the primary and secondary (recall) humoral responses to
antigen (see Figure 15). The immunization schedules are described in detail in experiment 1-1
and in Figure 15, and we include preliminary data showing that a 4 week rest period is sufficient
to complete the primary IgG and IgM response to tetanus toxoid (Figure 14).
2) “Also, there is no mention of what adjuvant will be used.” The tetanus toxoid preparation to be
used for immunizations will be alum-adsorbed (aluminum hydroxide). This is a commonly used
adjuvant for tetanus toxoid immunizations1. Details have been incorporated into the Methods
section.
Response to reviewers
•Valid concerns: agree, address and fix, and locate
changes for the reviewer
5) “The strength of the studies in this specific aim [2] is that they will be phenotyping innate and
adaptive immune response changes in response to infection. Their proposed approaches include
RNAse protection assays and serum cytokine bead array studies…However, it is not clear at what
time points they will be making their determinations.” We regret the lack of detail originally
provided and have incorporated this information. We will examine cytokine responses in
tissues and sera 2, 3, and 4 days after wound inoculation, which will permit an examination of
cytokine responses 24 hours prior to and during the time frame of mortality due to burn wound
infection. The rationale for these time points is provided in the Research Design and
Methods section under experiment 2-2.
Response to reviewers
Invalid concerns: delicately disagree and thoroughly defend
*remember: maybe you didn’t explain it clearly enough!
6) “The last specific aim will address which cell populations are involved in the beneficial effects of
FLT3L treatment…. If successful, this approach will indicate whether DCs alone are responsible for the
improved immunity following FLT3L treatment or whether it is due to increased NK cell function.
However, there are many adoptive transfer studies proposed with no supporting information to indicate
that these studies are feasible….Since these studies will depend mostly on successful adoptive
transfer, more supporting information is needed to verify the feasibility of these proposed studies.”
We have included new data showing the presence of CFSE-labeled dendritic and NK cells in the
spleen (Figure 10) 48 hours after i.p. injection. In addition to demonstrating the presence of
transferred cells after i.p. injection, we demonstrate a functional effect after i.p. transfer of dendritic
cells (protection from lethal wound infection, figure 10) and have previously demonstrated a functional
effect after i.p. transfer of NK cells (restoration of mortality after rapidly lethal CLP in β2-microglobulin
mice treated with anti-asialoGM1)2. Although intravenous transfer of cells is common, the use of i.p.
injection for adoptive transfer is not uncommon and has been reported for transfer of numerous
leukocytes including macrophages3, dendritic cells4, T cells5,6, and total splenocytes7,8. One
group performed a direct comparison of i.p. and intravenous administration of B cells and found no
differences in the trafficking patterns or level of tissue reconstitution9. Our preliminary data indicate
that enough dendritic and NK cells can be transferred by intraperitoneal injection to be visualized in
the spleen and, most importantly, to induce a functional effect.
Response to reviewers
• Invalid concerns: delicately disagree and
thoroughly defend
• *Remember: maybe you didn’t explain it clearly
enough!
6) “One concerning aspect about this aim is the animal studies proposed in aim 3.5. All of their
work has been completed thus far in BALB/C mice. They state that the transgenic mice have
been bred onto the BALB/C background but it is important that the controls for these studies are
appropriate for the experimental group.”
The CD11c-DTR transgenic mice were bred on a BALB/c background so we anticipate similar
responses to Flt3L, burn, and wound infection in the CD11c-DTR mice as in the BALB/c mice that
were used in our prior studies. Nonetheless, as stated in the methods, control groups will
consist of CD11c-DTR transgenic mice that will be treated with Flt3L but not injected with
diphtheria toxin, and CD11c-DTR mice that receive no Flt3L and no diphtheria toxin prior to
wound infection. We have expanded the description of these control groups in the research
design section (experiment 3-5).
Revisions
• Clearly mark revisions in the application
(underline, italics, margin lines)
• Be especially thorough, since the
reviewers will focus most of their time on
revisions versus entire application
• Remember, this is your only
communication with the reviewers, and you
only have two more chances to submit!
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Grant Resubmissions:
Senior scientist and study section
perspective
Satish Srivastava, PhD
Professor
Biochemistry & Molecular Biology
Grant Resubmissions:
Overview & Summary
Miles Cloyd, PhD
Professor
Microbiology & Immunology
Research Services
Thank you.
Questions from the audience.