How do I write grants for CB8500 and beyond

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How do I write grants for CB8500 and beyond?
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How do I write grants for CB8500 and beyond?

• Note that there are different and apparently
  equally successful writing styles
• Some differences boil down to personality and
  taste
• This summarizes some lessons learned by Boris
  while writing and reviewing grants
• Take it with a grain of salt, and extract
  thoughts that might help your personal writing
• Good writing can be learned! Or on a more
  realistic note, writing skill can be improved.
• What do you want to know?

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The grant writing reviewing process

• Investigators submit proposals to an agency or
  foundation (usually following a prescribed
  format)
• Agency assembles a group of peers to review
  proposals (not all reviewers will be close to
  your area of research)
• Reviewers read grants and produce a written
  review
• Reviewers meet and discuss proposals and
  establish a merit ranking
• Agency makes funding decision taking ranking into
  account
• Applicant receives decision along with critiques
  and if not funded prepares an amended application
  taking the input into account.

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What are the two most important questions before
you start most professional writing?

• What do I want to achieve? (The clearer you
  understand where you want to go the easier it
  will be. When in doubt during the process,
  measure against the goal)
• Who am I writing for? (This is important to find
  the appropriate level of formality, technical
  detail, argument to focus most heavily on, etc.)

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What do you want to achieve in a grant proposal?

• You want it funded! After reading your grant the
  reviewer has to want to be your advocate and
  lobby hard for your grant, for him/her to do so
  you need the reviewer
• To understand your research plan to the fullest
  extent possible -- with little effort on his/her
  side
• To understand that this is an exciting new idea
  that pushes interesting science and has important
  implications beyond (medical, economic, you name
  it)
• To understand that you happen to be exactly the
  right person to take this on

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Good Science versus Good Grantsmanship?

• Often a strong distinction is made between the
  ability to do good science (as in perform
  experiments at the bench) and to write well in
  particular write grants well
• Personally, I am not sure that the difference is
  as big as people make it
• Once the arguments and experiments are all clear
  and straight in your head the grant is easy to
  write
• So why then is serious writing so hard and
  exhausting for most of us?

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Good Science versus Good Grantsmanship?

• Because the arguments and ideas often are not yet
  all clear when you sit down to write!
• Try to perceive grant writing more as a
  continuous creative process rather than banning
  something on paper that already exists
• Stay flexible and willing to change!
• If you cant write about it convincingly, you
  should consider that it might not be convincing.
• Isolate the argument that is causing you trouble
• What could be changed to overcome this (drop or
  add experiments, reframe the question, read up on
  additional background or different approaches)?
• An outstanding proposal combines great ideas with
  flawless presentation and an engaging tone

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From idea to proposal to review

• Some thoughts on picking a topic for your grant
• The standard RO1 format
• Grant segments blow by blow
• A quick outline of the review process, a study
  section meeting, and the criteria of a written
  review

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How am I supposed to come up with a new and
original idea?

• Find an area, phenomenon, organism, or disease
  you are really interested in. Enthusiasm is
  important for your creativity and an important
  area of strength of your proposal.
• Look at the recent literature and establish
  whats known.
• Based on that assemble a list of unsolved
  questions
• Can you build a hypothesis that potentially could
  address your question
• (you can train yourself by coming up with a
  specific aim for each paper you read just ask
  yourself what next)

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How am I supposed to come up with a new and
original idea?

• How could one test your hypothesis?
• Develop experiments, weigh and prioritize
  different approaches
• Rank your questions as to how important and
  interesting it would be to find the answer and
  compare that to how hard it would be to get there
• The perfect grant addresses an important problem
  and looks so doable that you wonder why nobody
  has done that already

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How am I supposed to come up with a new and
original idea?

• Write a rough draft of your specific aims
• Try to find flaws in your ideas and read up on
  the approaches you propose to use
• Look at it as you would as a reviewer is this
  really convincing, do we care, can it be done? Be
  critical and honest with yourself.
• Get some peer input at this stage (if you wait to
  the end you have little time for major
  adjustments). Many people will agree to read over
  a 1 pager, 25 will require more commitment.
• Draft your Background, then go into your
  experiments. Reading background will help you to
  develop a clean rationale.
• Write your summary last. Make sure your summary
  is not too listy or technical, but confers in
  broader strokes the vision of your research
  program, your enthusiasm for these ideas, and the
  timeliness of your proposal

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The NIH RO1 format

• This is one of the main mechanisms of support of
  biomedical research in the U.S.
• RO1 proposals can respond to a call for specific
  proposal (so called program announcements) or be
  investigator initiated
• They outline a plan for a substantial research
  effort that (in most cases) tests a set of
  hypotheses to answer a question of biomedical
  relevance
• This relevance can be broad or narrow (NIH
  funding is not restricted to applied projects)
• It provides support for up to five years to a
  level of 250,000 per year
• (While there are differences in length and
  specific structure between agencies most grant
  proposal follow a similar general outline)

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The NIH RO1 format

• Front page(s) with lots of technical detail on
  funds requested, period of support, indirect
  cost, signatures, etc.
• Abstract
• Biographical sketches of key personal
• Resources
• Specific Aims
• Background and Significance
• Preliminary Studies
• Research Design and Methods
• Regulatory concerns (animals, human subjects,
  safety)
• Literature
• Letters of support, manuscripts that are accepted
  yet not available yet
• Currently the core narrative has a page limit of
  25, however, this will go down to 15 by the end
  of the year

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The abbreviated CB8500 format

• Abstract (300 words)
• Specific Aims (1 page)
• Significance Background (4 pages)
• Experimental Plan (2 pages)

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Specific Aims

• Start with a paragraph that highlights the
  significance of your area of research and provide
  critical background and preliminary data to make
  sure the reviewer understands your aims. This
  should be heavy on rationale. Answer the
  reviewers question Do I really want to read 25
  pages of this stuff?
• Specific aims should be specific -- yet not
  technical
• When you construct your specific aim try the
  biology first rule.
• Put the biological question and/or hypothesis
  first, then provide the technical solution

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The Biology First rule, lets look at an example

• Aim 1 Flow-cytometric analysis of lymphocytes
  from mice infected with T. cruzi.
• Aim 1 Identify lymphocytes critical for the
  control of T. cruzi infection.
• Aim 1 Which subgroup of lymphocytes is critical
  for the control of T. cruzi infection?
• Check your draft with the rule in mind!

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The anatomy of a Specific Aim -- or any bit of
scientific writing

• Title (which includes a question or hypothesis).
  Rationale. Question. Hypothesis. Approach (keep
  it simple yet convincing). Expectation towards
  outcome/ What next?
• Aim 1 Does the Biology First rule improve the
  funding success of NIH grant proposals? Attaining
  funding is a critical hurdle in the career of new
  investigators. However, firm rules on how to
  write successful proposals are currently missing.
  Based on the results of a preliminary survey of
  55 new investigators we hypothesize that putting
  biology first is an important part of a winning
  strategy. To test this idea we will
  experimentally evaluate the response of reviewers
  to paired specific aims which do or do not use
  the Biology First rule. As controls (don not go
  overboard on the detail) We expect that this part
  of our study will provide a robust and
  statistically significant evaluation of the
  Biology First rule. A validated Biology First
  rule could provide an important tool fostering
  the careers of numerous young scientists.

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Background Significance

• Write a clear and clean introduction into your
  area of research. The reviewer has to understand
  the science to be able to follow -- and
  appreciate the cleverness of your experiments.
• Make it obvious why this area is important and
  interesting.
• Be sure to cite mostly primary research. Limit
  reviews and stay away from web sites. This is
  your opportunity to demonstrate that you are well
  and broadly read and that you know your stuff.
  Dont cite papers you have not read -- fact
  check!
• Nothing is as deadly as writing things that are
  obviously wrong
• A lot rides on your reputation, do not tarnish it
  by using poorly researched factoids!
• Use figures, but dont show obvious things but
  focus on areas likely new to the reviewer
• If you use figures make sure that they are simple
  and easy to follow (dont use bits of your last
  paper that flood the reviewer with distracting
  data)

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Background Significance

• Don not just fill a few pages with facts and
  citations around your topic!
• Clearly outline what is known and what not
• Use the BS section to build momentum towards
  your new project.
• Surprisingly, later on your research will address
  some of the most important still open questions.
• You can finish some of your sections by pointing
  out that in Aim 3 of this proposal we will
  elucidate the mechanism of this phenomenon by
• The overall goal is to have the reviewer agree
  that this is interesting and have him or her feel
  that the work you suggest is a reasonable if not
  a natural extension of previous work by you and
  others in your field.

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Preliminary data

• The preliminary data section describes work you
  have already done and that the reviewer should
  consider in thinking about your proposal
• This can be published work (in a condensed
  version) but often features data that are not yet
  publically available
• Preliminary data come in different flavors
• Data that motivated you to initiate a research
  project and frame the backdrop for the rationale
  and/or the question
• Data that support your hypothesis
• Data that suggest that your approaches are
  feasible
• Data that exemplify the type of studies you plan
  to do

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Preliminary data

• Do not hide good data, but also do not distract
  the reviewer with a flood of data
• Make clear arguments with your data
• Do not present data that you do not believe
  yourself!
• Seriously, if you cant make a convincing case,
  dont go there
• Preliminary data are an important part of your
  reputation with the reviewer. They also give the
  reviewer the opportunity to evaluate your
  judgment
• Dont be timid but make clear that you understand
  all the caveats and alternative explanations
• If you dont know something say so and point out
  how the proposed work will clarify the issue

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Experimental Plan

• This is the place to flesh out your specific aims
  with real experiments
• Basically follow a more detailed version of the
  specific aim anatomy.
• Essentially you write this like a paper, you just
  dont have the data yet.
• You still can construct arguments, weigh evidence
  etc.
• Do not provide a boring technical run down of
  your experiments!
• Make sure the rationale for doing an experiment
  is always clear, remember the Biology First
  rule. Lead with the problem, then provide the
  solution.

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Experimental Plan

• You have to convince the reviewer that the
  methods are appropriate, that the experiments
  have a high likelihood of success and that you
  are well versed in these approaches
• Make sure that your experiments test the
  hypothesis and that you provide a specific
  expectation towards the outcome
• Discuss different possible outcomes and make
  clear how such results would impact your
  hypothesis and how that will change your plans.
• What if your approach fails? Provide a discussion
  of potential pitfalls or problems and offer
  solutions to these problems or back up strategies
• If your strategy is complicated a figure might
  help the reviewer to understand it.

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How to handle technical detail (especially in the
experimental plan)?

• Be mindful of the diversity of reviewers
• Some will hear about your area for the first
  time, while others are the worlds expert on the
  subject
• Your writing has to please convince both camps
• Dont loose the generalist, and let enough
  technical sparkle shine through to convince the
  specialist that you know your stuff
• How can you have it all in one document?

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How to handle technical detail (especially in the
experimental plan)?

• Ogres have layers! Try to write an onion.
• Start the Aim/Subaim with a discussion of the
  rationale/question
• Summarize your technical solution in a way
  everybody on the panel should understand (e.g. we
  will test importance by constructing and
  analyzing mutants)
• Then dive into the nuts bolts (how exactly will
  you make the mutants)
• Wrap up with a discussion of what you will have
  learned that again is conceptual and not
  technical
• The beginning and end is for everybody the center
  targets the specialist, make sure that the
  generalist reviewer can understand beginning and
  end without the center

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The Finish line

• Make sure you have sufficient time to finish
• Proposals riddled with typos and grammatical
  errors come across as sloppy and annoy the
  reviewer
• Make sure your references are complete and
  correct.
• Have a copy editor!

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Random thoughts on style

• Obviously different folks write differently
• Some simple things
• You do not hope you expect
• Active can be more engaging than passive
  (phenotypes will be analyzed by We will analyze
  the phenotypes)
• Every time you want to write make, do, look
  think if there might not be a more specific and
  polished term at your disposal

• Let your enthusiasm shine through, find the level
  of hype you personally are comfortable with
• Respond politely and constructively to reviewer
  criticism
• If they did not understand something, do not
  point out that they are idiots, apologize for
  making it not clearer and then do a better job in
  constructing the argument
• You can not fight the reviewers you have to win
  them over

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Some web-resources

• http//webs.cb.uga.edu/Estriepen/biopara/cb8500gr
  ants.html
• http//www.hfsp.org/how/ArtOfGrants.htm
• http//www.niaid.nih.gov/ncn/grants/default.htm

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Reviewing grants what happens after your submit?

• We will split into two review panels (called
  study section at the NIH)
• Each grant will receive a formal written review
  from two reviewers assigned by a Scientific
  Review Officer (me)
• The panel meets and discusses each application
  (in real life there is often some kind of triage
  process to reduce the work load during the
  meeting
• Every member of the panel has an equal vote in
  assigning a score
• (We will simplify the process each panel member
  provides a ranking 1 best proposal)

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Reviewing grants typical discussion

• Reviewer state preliminary scores (we wont do
  that)
• The primary reviewer provides the panel with an
  overview of the grant (quickly summarizes the
  main ideas approaches), then he/she discusses
  the main strength and weaknesses of the proposal
• The secondary reviewer provides his/her review
  focusing in particular on areas that differ from
  the primary review
• Panel members ask questions and voice opinions
• Reviewers address those
• Chair summarizes discussion
• Panel votes

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Categories addressed in NIH reviews

• SIGNIFCANCE Is this important?
• APPROACH Is the approach sound?
• INNOVATION Does this bring anything new to the
  table?
• INVESTIGATOR Is the PI and his/her team
  qualified to pursue this project?
• ENVIRONMENT How good is the environment for this
  type of work?
• OVERALL EVALUATION A paragraph that brings it
  all together

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Reviewing grants

• Being asked to review grants is an honor, can be
  a pain, and almost always is a lot of work
• You should take your role as reviewer (in this
  class and elsewhere) seriously
• Try to be candid yet polite
• Edit your review for emotionally colored language
  (on page 9 finally an original idea, the lack of
  data is annoying )

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Reviewing grants

• This is a video production from the NIH that
  shows a typical study section http//cms.csr.nih.
  gov/ResourcesforApplicants/InsidetheNIHGrantReview
  ProcessVideo.htm
• NIH Reviewer instructions http//cms.csr.nih.gov/
  resourcesforapplicants/policyprocedurereviewguide
  lines/