Research Services presents

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Research Servicespresents
Study Section TrendsRe-submissions Emcee Toni
DAgostino, Director, Office of Sponsored Programs
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Study Section Trends

• Agenda
• Welcome, Announcements and Introductions
• Panelists Presentations
• Discussion

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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

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Grant Resubmissions Approach to critiques and
revisions Tracy Toliver-Kinsky, PhD Associate
Professor Anesthesiology
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Grant Resubmissions Approach to critiques and
revisions

• Call your program director
• Response to reviewers
• Revisions

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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

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Grant Resubmissions Approach to critiques and
revisions
Step 1 Call your program director
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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

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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.
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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
• 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.

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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 studiesHowever, 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.
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Response to reviewers
Invalid concerns delicately disagree and
thoroughly defend remember maybe you didnt
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
ß2-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.
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Response to reviewers

• Invalid concerns delicately disagree and
  thoroughly defend
• Remember maybe you didnt 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).
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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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Good luck!






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Grant Resubmissions Senior scientist and study
section perspective Satish Srivastava,
PhD Professor Biochemistry Molecular Biology
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Grant Resubmissions Overview Summary Miles
Cloyd, PhD Professor Microbiology Immunology
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Research Services

• Thank you.
• Questions from the audience.