Principles of Grant Writing

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Principles of Grant Writing
Allison B. Reiss, M.D. Head, Inflammation
Section Winthrop University Hospital
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Getting Started

• Find a mentor
• Select an area of interest
• Read the literature in the field
• Ask questions
• Look for gaps in knowledge
• Come up with a novel idea
• Generate a meaningful hypothesis
• Secure collaborators for areas in which you lack
  experience/training

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Being a Credible Candidate- Your CV

• Gather preliminary data
• Publish with your mentor
• Write review articles or book chapters
• Present abstracts
• Attend scientific meetings in the field
• Network
• Join committees
• Follow NIH biosketch format

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Choosing a Starter Grant

• Start modestly and expect criticism
• Local societies such as LI Chapter of Arthritis
  Foundation or American Heart Association
• Fellowship grants with mentor
• R03- small grants for new investigators
• Small specialized foundations
• Always adhere to the requirements of the grant
  solicitation.

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Getting Organized

• If it is your first time start 3 months ahead!
• Read the instructions for the specific
  application
• Be sure that you qualify- stage of training,
  academic appointment, degree necessary,
  citizenship requirements
• Be sure that your grant fits the stated
  objectives of the program
• Make a checklist of all the things you need to
  accomplish- you can have the body of the grant
  completed, but without the ancillary paperwork
  you will miss the deadline!

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Title

• Come up with an attention-grabbing title that
  communicates the key points and focus of the
  application. This is your FILM and you want to
  win the Oscar for best picture!!
• Reviewers may have to judge their ability to
  review an application based solely on the title.
  They are often asked to rate their expertise from
  1 (this is my field) to 5 (I am clueless) based
  on title alone or title and abstract
• You do not want your application to be read by
  someone who will not be able to understand and
  appreciate your ideas.

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Sections of the Grant

• Abstract
• Specific Aims
• Background and Significance
• Preliminary Data
• Research Design and Methods
• Other (depends on grant)
• Human subjects
• Vertebrate animals

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Specific Aims

• These are the objectives of your research
  proposal
• Most important- set the tone for the whole grant
• First thing reviewers evaluate
• Should be driven by a strong hypothesis
• Usually two or three per application
• Should be focused and coherent

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Specific Aims- Format

• State the aim in bold type- be succinct
• Add a sentence or two describing the rationale
  for the aim and the methods to be used.
• The Specific Aims should not take up more than
  one page.
• Do not be diffuse- aims should be feasible and
  relate directly to hypothesis
• Do not turn the aims into a list of experiments
  or your grant will be triaged!

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Specific Aim Example from NIH-Funded Application
entitled Immunological Mechanisms in Premature
Atherosclerosis

• Examine the impact of immune reactants in the
  circulation of SLE patients on cholesterol
  homeostasis in cells relevant to atherogenesis.
  Effect of SLE patient plasma on expression of
  proteins involved in cellular cholesterol uptake
  and excretion (27-OHase, ABCA1, ABCG1, LOX1, LDL
  receptor, scavenger receptor) is assessed
  (Western blot, Quantitative real-time reverse
  transcription-polymerase chain reaction
  QRT-PCR) in the THP-1 human monocytes and human
  arterial endothelium. Relative contribution of
  IC-C1q and IFN-gamma present at elevated levels
  in SLE patient plasma to? the decrease in
  27-OHase message is evaluated by exposing cells
  to SLE plasma with/without specific
  immunoneutralization (achieved by pre-incubation
  with anti-C1q receptor antibody, anti-IFN-gamma
  antibody and anti-IFN-gamma receptor antibody).

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Background and Significance

• Your chance to set the stage- be convincing,
  compelling, succinct, thorough.
• State problem to be investigated and rationale
  for proposal. Logical persuasion.
• The scientific question- what has been published
  by others in the field? Show that you have a good
  command of the current and ongoing research in
  your field.
• What is not known and why is it important to fill
  in the gaps or resolve discrepancies?
• How will your proposed study advance knowledge
  and resolve issues in the field- groundbreaking?

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More on Background and Significance

• Demonstrate that accomplishing your aims will
  provide new information that fills in crucial
  holes.
• Have you already made contributions?
• Emphasize the innovative nature of the work and
  impact you have made or will make.
• Be sure to reference prominent scientists in the
  field- they may be reviewing your application!
• Dont write a review article- you need to save
  space for your methods section.

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Preliminary Data

• Your opportunity to show that you are technically
  competent to design and carry out meaningful
  experiments.
• Data from replicate experiments with good
  reproducibility, small error bars, carefully
  analyzed, properly controlled.
• You must present results clearly, completely and
  objectively.
• Charts, graphs, tables, statistics are key.
• It is crucial that your data provide a sound
  basis for the proposed hypotheses.
• Evidence that the proposed techniques will work
  and that you can perform them.

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Research Design and Methods

• Heart of your plan- describe your methods and
  experiments in detail.
• Correspond methods to each aim in turn.
• Exactly how results will be collected, analyzed,
  interpreted.
• Include the results you expect and their
  significance and relationship to your
  aim/hypothesis.
• Describe what it will mean and what you will do
  if you get unanticipated results.

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Research Design and Methods contd

• Discuss potential difficulties and limitations
  and how these will be overcome or mitigated. Need
  alternative approaches.
• Specify animal models, exposure times, reagents
  and how you will obtain them, statistical
  analysis methods, and other details.
• Are these the optimal most suitable methods to
  compile the data you need? If possible, discuss
  other methods and justify your choice.
• Give context- dont just list methods. Are
  methods direct extensions of your preliminary
  data?
• Include a timeline.

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Pitfalls and Alternatives

• The experiments proposed are a logical extension
  of our previous work in which we demonstrated a
  highly significant downregulation of 27-OHase
  mRNA expression in cultured human arterial
  endothelium after 3 hr of exposure to SLE patient
  plasma (see Preliminary Studies). I have
  extensive experience in formulating and executing
  this type of study. The study will be blinded so
  that the person measuring 27-OHase levels will
  not know which human plasma and antibody
  conditions the cells were subjected to. That
  information will be kept confidentially with
  numerical coding.
• The following difficulties may arise 27-OHase
  downregulation by SLE patient plasma may not be
  blocked by blocking C1q or IFN-gamma. SLE is
  characterized by the production of multiple
  autoantibodies. Although the pathogenesis of SLE
  remains enigmatic, autoantibodies against dsDNA
  and ribonucleoproteins, deposition of IC,
  complement activation, and leukocyte infiltration
  are thought to represent a consequence of immune
  dysregulation in this disease. Thus, a number of
  factors in plasma are potentially involved in
  regulating the 27-OHase. If blocking IFN-gamma
  and IC fails to ablate downregulation, we will
  look at downstream effectors in the complement
  cascade (i.e. complement components C3b, C3bi,
  C5a and their receptors or C5b-9). This will be
  accomplished using antibodies to CR1 and CR3 or
  the receptor for C5a or antibodies to C3b, C3bi,
  or C5a.

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Research Environment

• Must establish that the facilities, resources and
  personnel are favorable for execution of the
  project aims.
• Describe the scientific environment and emphasize
  the features that you need and their ready
  availability.
• Institutional support- letter from chair/director
• Collaborators/consultants- get the best. Most are
  approachable and helpful. Their strong CVs will
  enhance you!

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Human Subjects

• Can be tricky and sensitive
• Be sure to stay within HIPAA guidelines
• Minimal discomfort/risk to patient
• Confidentiality and privacy of subjects must be
  maintained
• Informed consent
• Participation must be voluntary- discuss risks
  and benefits

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Elements of Human Subject Study

• Description of population to be studied
• Description of method by which subjects will be
  identified and recruited
• Sample size
• General purpose of the investigation
• Source of research material
• Subject inclusion criteria
• Subject exclusion criteria
• Duration of study
• Inclusion of women, minorities
• Inclusion of children
• Data and Safety Monitoring Plan

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Budget

• You need to know your stuff!
• Get salary guidance from human resources- many
  grants limit salary
• Must look up expenses of your major supplies such
  as glassware, cells, enzymes, antibodies, assay
  kits, animals and their chow/care etc
• Can get this info online or in catalogs or call
  the company.
• The higher percent effort you can give the better.

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Grant Killers- Reviewer Turn-offs

• Significance is unclear So what?
• No innovation is noted
• Proposal is not hypothesis-driven, but is a data
  gathering exercise
• Over-ambitious, dense, diffuse
• Preliminary data is not convincing/clear-cut
• No back-up plan
• Would never pass IRB
• Lacks statistics, power calculation

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Proofreading

• Final draft of a proposal should be proofread by
  someone other than the primary grant writer.
• Ask other successful investigators to proofread
  your grant and provide feedback. 
• Make sure your grant is grammatically correct.
• Check spelling and punctuation.
• Look for errors in logic or presentation.

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Submission

• Check the deadline. Late proposals not
  considered.
• Make sure font size, margins and length are
  within guidelines.
• Page limitations
• Administrative approvals-Sponsored Programs will
  help. Let them know early.
• Letters from consultants/collaborators
• Manuscripts/publications
• Cover letter
• Electronic or delivery service or both? File
  format.
• Web sites can get jammed near deadline.

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Good Luck!!

• If you need help, you can contact me through AFMR