Transcript How to Craft a Well-Written Grant Proposal

How to Craft a WellWritten Grant Proposal
MBP 1018Y
Introductory Lecture
January 09, 2008
Outline
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Components of a good grant
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Generating appropriate hypotheses
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What grants are evaluated based on
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The science in a good grant
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Translational application
“The Matrix”
GOOD WRITING
GOOD WRITING
GOOD SCIENCE
BAD SCIENCE
BAD WRITING
BAD WRITING
GOOD SCIENCE
BAD SCIENCE
Components of a
Successful Proposal
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Abstract
Introduction/Background
Specific Aims
Hypotheses
Methodology
Probable Outcomes/Contingencies
Translational Application
Significance
Conclusions
Abstract
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Not counted in the page limit
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Should be concise, clear, easy to read
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Within 250 words, describe the
relevant background, your goals, and
proposed study design, as well as the
relevance and impact of your research
Introduction/Background
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Review the RELEVANT literature
This is not meant to be an exhaustive
literature review, but rather a discussion of
what is most important to what you want to
do
Provide background for the disease and
questions you will be addressing
Also provide background about any novel
technical approaches
Include a succinct rationale for the project
(concept and approach)
Specific Aims
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Should address:
– What are the major questions your
project is designed to address?
– What are the objectives of your
project?
– How will each objective address the
project-specific questions?
Hypotheses
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VERY IMPORTANT TO INCLUDE
THESE!!
Each hypothesis should correlate,
where possible, with a specific
objective or question being addressed
EXCEPT when you are addressing a
technical objective (e.g., the creation
of an experimental system)
Methodology
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Describe your experiments in detail
Focus on study design
– Study design should match up with
objective
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Reference previously established
techniques, except for specific
modifications
– For example, no need to describe RNA
isolation in detail…unless that’s your
project!
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Need to address where your samples
are coming from
Probable
Outcomes/Contingencies
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What do you expect to observe?
What are your plans in case your experimental system
goes awry?
You should not merely describe your experimental
plan – the reader would not be expected to know how
the studies are supposed to turn out
Under what circumstances will your hypothesis be:
– Proved?
– Disproved?
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What will you do if something doesn’t work out that
the rest of the project is dependent upon?
Translational Application
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How is your project relevant to the human
condition, and to patients?
Describe the relevance and importance of
your work to the diagnosis, prevention and
treatment of cancer or the appropriate
disease
Be careful – sometimes use of patient
samples is not sufficient for translational
application!
Conclusions
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Be brief!
Restate your goals, hypotheses and
expected outcomes
Underscore the importance of your
work
Make the “big picture” connections
Feasibility of Studies
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Most grants are funded for a 2-5 year
timeframe
You need to ensure that, whatever you
propose, it can be accomplished within that
window
– Aim for 3 years, knowing that you have margin for
error in that regard
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Be careful about # samples and types of
experiments you propose
– For e.g., a microarray study on a cohort of 100
patients, prospectively over time (collecting 5
samples total) amounts to 500 array experiments,
plus controls!
– For Affymetrix GeneChip expression arrays, that’s
easily $300K
Referencing
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Be consistent in terms of style
# references provided are often
an indicator of effort put into
proposal development
At a graduate level, anything less
than 20 references is NOT
acceptable
Hypotheses
Hypotheses
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Are supposed to be falsifiable
Can be specific
It’s OK if they end up being
WRONG!
Hypotheses MUST agree with the
objectives under investigation
A Bad Hypothesis
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Objective:
– To determine the association between
Gene X and patient outcome in AML
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Hypothesis:
– Gene X is associated with AML
– Gene X is involved in the DNA damage
response
– AML patients that demonstrate impaired
DNA damage have a poor prognosis
A Good Hypothesis
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Objective:
– To determine the association
between Gene X and patient
outcome in AML
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Hypothesis:
– Expression of Gene X is associated
with poor prognosis in AML
What Grants Are Typically
Evaluated Based On…
Proposal
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Clear, testable hypothesis or central
research problem
Originality and innovation in concept
or approach
Significance and relevance to health
Feasibility of work plan, usefulness of
results
Knowledge of the field (cited
literature)
Clarity
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Grant should be written as if it were directed
at a general scientific audience
You are the most knowledgeable person with
respect to what you have written
Do NOT make assumptions about what the
reviewer knows or not
Be CLEAR
EXPLAIN yourself
Your work should be able to be intuitively
followed by the reviewer
When Writing a Grant…
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…Explain:
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WHAT you want to do
WHY this is a reasonable thing to do
WHY this is important
HOW you will do it
WHO is going to benefit
WHERE samples will be obtained from
WHEN you expect to have data
Explain…
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What you want to do
– central hypothesis/research question: the big idea
– plus specific objectives
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Why this is a reasonable thing to do
– review of previous work by you and others,
– succinct rationale for project (concept and
approach)
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Why this is important
– significant new knowledge to be obtained
– improvements to health which will result
Explain…
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How you are going to do it
– detailed work plan, logical sequence and
timelines
– analysis and interpretation of results
– pitfalls and ways round them
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Why you should do it
– relevant prior experience and skills
– collaborators for technical gaps
– preliminary data showing feasibility
What to Make Sure You
Do When Writing A Grant
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Follow formatting guidelines carefully
– 10 double spaced pages
– Page count does not include figures, tables,
references
– 1” margins
– 12 point font
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Include a Title Page
Include Page #’s!
Include section headings
Include your hypotheses, clearly stated
Clearly delineate your goals and study
designs
Reference your work carefully
Before Submitting your
Proposal
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PROOFREAD!
Spelling/grammar and wording or style
errors will impair the readibility of your
proposal
Avoid:
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Run-on sentences
Short paragraphs
Grandiose claims
Colloquial phrasing
Vague wording
Evaluation Criteria for
Final Exam
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Translational nature of proposal: Inclusion of a translational
aim
Significance section (40%)
Conciseness and appropriateness of introduction
Clearly stated goals and hypotheses
Delineation of experimental design
– Logical, easy-to-follow, one step leads directly and intuitively
from the previous one
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Feasibility
Quality of Science
Minor criteria:
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Quality of abstract
Clarity of writing
Effort put into proposal
Formatting and referencing
Spelling/Grammar
Subjective “Style”
The Science in a Good
Grant
A Note About The Science
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For the 1018 Final Exam, you are
encouraged to base the grant proposal
on your current research
You are expected to have “good
science” in your proposal already
– Egregious errors will be penalized
– For e.g., Northern Blots used to detect
protein samples
Good Science…
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…Answers a well-defined
question
…Will contribute to human
knowledge
…Has falsifiable hypotheses
…Recognizes its own limitations
…Is well thought-out
Case Study: The Cancer
Stem Cell Hypothesis
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What is the Cancer Stem Cell Hypothesis?
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Modeled on normal development (e.g.,
hematopoiesis)
– A small fraction of cells in the tumor have the
capability to give rise to the tumor
– These cells are – in contrast to the bulk tumor
population – not in cycle, and often not treatable
by conventional chemo- or radio-therapy
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In contrast to the “Stochastic Model” of
Cancer Development
Cancers Known to Follow
the CSC Hypothesis
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AML
Brain
Breast
Colon
Others?...
How Do We Identify a
CSC?
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A Stem Cell can only be identified
FUNCTIONALLY.
A CSC can only be identified
through its ability to recapitulate
a tumor in vivo.
Appropriate Functional
Assay
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Flow sort tumor cells based on cell
surface markers
– Potential enrichment for CSCs in one
population over another
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Xenotransplantation into immune
compromised mice
Score tumor development
Examples of Inappropriate
(Inconclusive) Assays
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In vitro colony formation assays
– Assay of transformation
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Gene/protein expression analysese
– Expression microarrays
– miRNA arrays
– Immunohistochemistry
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Identification of a “Stem Cell” signature
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In vitro over-expression/knock-down of
putative “Stem Cell” genes
Translational Oncology
What is Translational
Research?
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For the purposes of this grant, “Translational
Research” is defined to be use of clinically obtained
samples in at least one major aim of the proposal
Specifically, use of:
– Human subjects (with malignancy or disease)
– Primary tissues/fluids (e.g., bone marrow samples or
tumour biopsies) derived from patients with malignancy
or disease
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You CANNOT use for this purpose:
– Mice or other animal models
– Cell lines derived from patients
– Other cell culture systems
But I Don’t Do
Translational Research!
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Don’t worry! Fewer of us than you might
think do purely translational research
Objective of MBP 1018 is to develop your
ability to conceive of and integrate
translational concepts into your thinking
If you do:
– Basic research (with cell lines or animal models)
– Structural research
– Photonics or imaging research
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…There are translational applications in the
future – just think about them!
But I Don’t Do Oncology
Research!
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That’s OK – think about the pathways you
work on.
Do they have application to cancer in some
way?
Can you draw connections outside of your
own immediate sphere of research?
If you can, write about those connections.
TA Contact Information
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Dr. Mahadeo Sukhai
Email: [email protected]
Phone: 416-946-4501 x 5036
Location:
– PMH/OCI 610 University Ave.
– Room 9-620/9-621
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No set office hours; please check to
see whether I’m available before
coming to see me