So you want to
write a grant?
Edwin L. Bierman, M.D.
So You Want to Write a
Grant?
 What
is my topic?
 Who is my audience?
 When is the deadline?
 What are my chances?
 What now?
Get Assistance
 Colleagues
 Mentors
 Department
chairs
 Deans and associate deans
 Grants and Contracts offices
 Specific funding agencies
 grantdoctor@aaas.org
Significance
Choose your area of research pursuit
carefully!
 Is it relevant to human health/disease?
 Why is your idea important?
 Make a compelling case
 What will be different if your specific
aims are fulfilled?
 Will both science and people benefit?
 If the work is basic, don’t overstate the
clinical significance

Innovation
Establish the need in Background and
Significance
 How will what you’re doing improve on
what is already known?
 strategies, methods, interventions
 Avoid PAIDS, the ‘Paralyzed Academic
Investigator’s Disease Syndrome’!!!


Goldstein JL, J Clin Inv 78: 848-854, 1986
PAIDS
Particularly common among clinical M.D.
investigators
 Doesn’t spare the most intelligent, curious,
and ambitious
 Typically occurs early in the independent
phase of career development
 Often is manifested by repetitive
experiments in an alternative system
 What’s really new here?

PAIDS AVOIDANCE
 Basic
science training
 Technical courage
Important questions
 New techniques
 Avoid fossilization in what we already
know, e.g.


Michael Brown and Joseph Goldstein
• familial hypercholesterolemia
–LDL receptor mutations
Hypotheses and Specific Aims
 Focus,
focus, focus!
 Be as mechanistic as possible
 Avoid being too ambitious
 Limit number
 2-4 are best
 All should be related, but
 Don’t build one specific aim on
previous aims
Preliminary Data




Sufficient to make grant feasible, but not excessive
or irrelevant
 You have the gene/antibody/mouse/population
Be objective
Be graphic
 Figures/Tables should be able to stand alone
 in proximity to relevant text
Prove techniques are available and/or
collaborations are in place
 Letters are essential here!
Experimental Plan






Repeat Hypotheses/Specific Aims with
accompanying Rationale
Make no assumptions that reviewers know how
you intend to proceed
Justify sample size and analytical approach
Avoid excessive detail for methods
 Except for novel use of complex technologies
 Refer to relevant publications
 your’s or a collaborators’, if possible
Identify pitfalls and provide alternative
strategies if/when problems do arise
Provide a timeline
Budget
 Clarify
 Justify

In detail
 Carefully
consider % effort
 Avoid ‘to be named’
 Don’t ‘pad’

Science drives the request
Abstract

Not an afterthought


Sets the stage


Longer ‘shelf life’ than the rest of the
application
One page advertisement
Content
Brief background
 Hypotheses/Specific aims
 Significance


Fill the box!
Style
Critically important for readership
 Use #11 or 11.5 font size
 Keep paragraphs brief
 Use graphs/figures when possible
 Spacing!
 Bold, italics and underlining provide
needed emphasis
 Strategies for each
 Be consistent!

SPECIFIC AIM #1: TO DEFINE THE ROLE OF LPL IN THE PERIPHERAL NERVOUS SYSTEM.
Rationale and Hypotheses: Unequivocally, the only definitive way to determine whether or not LPL activity and/or
enzyme protein in Schwann cells is important to the biology of the PNS in vivo is to genetically eliminate the lipase
(P0 LPL -/-) and replace it with a catalytically inactive form of the enzyme (P0 LPL */-). In LPL mutant mice, changes
in nerve function and myelin content can be assessed. To further determine the role of the lipase, the response of the
peripheral nerve to nerve-crush injury will be assessed. It is expected that deficiency of the active lipase, but not the
enzyme protein, will result in reductions in both myelination and nerve conduction velocity, with a delayed response to
nerve-crush injury. In vitro, neurons from Schwann cell replete mice (LPL +/+), P0 LPL -/- and P0 LPL */- will be
examined to determine their ability to grow and sprout processes. Moreover, in primary Schwann cells from mice with
Schwann cell specific knockouts of LPL (P0 LPL-/-), there will be a reduction in myelination when co-cultured with
dorsal root ganglion neurons. In mice with a knock-in of the catalytically inactive lipase (P0 LPL */-), it is
hypothesized that the defect in myelination in vitro will also be largely eliminated. This effect will relate to the ability
of the inactive lipase to bind and internalize lipoprotein particles, and thereby provide fatty acids for myelin lipid
synthesis.
Experimental Approaches:
A.
Generation of Schwann cell specific LPL knockout (P0 LPL-/-) mice.
To generate P0 LPL-/- mice, inactivation of LPL will be achieved by using the cre-loxP DNA recombination
method, where the cre recombinase carries out the site-specific DNA recombination at a specific 34-bp sequence called
loxP. When cre recombinase is introduced into cells that have genomic DNA flanked with two properly oriented loxP
sites, the genomic DNA flanked by the two loxP is cleaved out. Therefore, LPL flox/flox mice, provided by Dr. Ira
Goldberg (see letter), will be mated with heterozygous P0-cre mice (Dr. I. Parada) that express the cre recombinase
specifically in Schwann cells (Phase 1). Identification of all mice will use PCR from tail tip DNA and primers specific
for the cre transgene, the floxed LPL and the deleted LPL alleles. Confirmation of all mice will also include
measurements of LPL mRNA by in situ hybridization and immunohistochemistry.
Before Your Grant is
Submitted/Reviewed

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
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Read, reread and read again!
 Don’t rely on spell-check only
Get input
 Former mentor
 Informed colleague
 Outside reader
Human subjects, vertebrate animals
Resources and environment
 Address all aspects of the application
Submit supplemental materials before deadline
Human Subjects
 Why
not animals?
 Safety, safety, safety!
 Women, minorities, children

Exclusions must be scientifically
based
 IRB
approval
Revised Applications



Wait weeks after review is received to respond
Acknowledge and respond to each
criticism/comment
 Rebut only if
 You’re certain a reviewer is wrong
 You have new data
Remember, triaged applications can be funded
the next round
 Address in detail ‘fatal flaws’
Grant Application
A good scientist is always pushing the envelope.
Best wishes in all of
your pushing!