Grant writing: Specific Aims
• Probably the most important part of
the proposal
• Need to grab the reviewers’
attention
• Summarizes the application - help
reviewer predict the rest of the
proposal
Dennis Brown, PhD, 2016
Dennis Brown, PhD, 2016
Specific Aims Page
• 1 page – make it look nice
• Introductory paragraph
• List of Aims (2-4 usually)
• Closing sentence or two (optional)
Dennis Brown, PhD, 2016
Introductory paragraph
• Attention grabbing first sentence
• Background information
• Knowledge gaps to be filled
• Why should we care?
Dennis Brown, PhD, 2016
Attention grabbing sentences
(from our applications)
• “Are humans an endangered
species?”
• “Our finding that AQP2
constitutively recycles… led to a
rethinking of the urinary
concentrating mechanism.”
Dennis Brown, PhD, 2016
Background information
• Say what you want to achieve (goal)
• Say what you have done (briefly)
(use “we have…..”)
• Tell them what you want to do and
why
• Briefly how.. any new method
Dennis Brown, PhD, 2016
The Goal of our work….
•
The overall goal of our work is to
understand the cell biology of
vasopressin (VP) signaling and aquaporin
2 (AQP2) trafficking in the kidney in
order to inform our translational efforts
in the area of water balance disorders,
including nephrogenic diabetes insipidus
(NDI).
Dennis Brown, PhD, 2016
What we have done….
• “Over the past three years, our work
has uncovered several important
and previously unrecognized aspects
of this process”
Introduce major findings: 1).., 2).., 3)…
Dennis Brown, PhD, 2016
What we have done….why am I the
person to do this work?
• New investigators – refer to (recent)
published data and add in relevant
major preliminary data
• For renewals – refer to work
achieved in previous funding period
and also relevant preliminary data
Dennis Brown, PhD, 2016
Mixture of published and new data
•
Our previous basic studies describing the use of sildenafil and
statins to bypass defective V2R signaling have recently been
validated in limited observations on human NDI subjects.
(positive use of past funding)
•
We have also applied an unbiased screening approach using our
novel trafficking assays to identify new drugs for the treatment of
NDI. (preview of the methods to be applied)
•
In this way, we recently found that AQP2 membrane
accumulation can be induced in cells and tissues by inhibiting
epidermal growth factor receptor (EGFR) signaling. We have now
found that Erlotinib reduces urine output by 50% in a rat model of
NDI. (new, exciting data)
Dennis Brown, PhD, 2016
Moving forward – what we propose
•
Thus, we consider the combination of informed and unbiased
screening to be a valid approach for the discovery of new
therapeutic avenues for various forms of water balance disorders.
•
We will use cell models and mice (or your methods of choice) to:
A)….., B)…….C)……. Brief summary of 3 aims, but using different
language
•
Summary sentence if desired, and what you expect to discover:
Dennis Brown, PhD, 2016
The Aims
•
Be specific and not vague or general
•
AIM 1: Define the intracellular pathways and signaling events that
regulate intracellular trafficking of AQP2 based on new data on
transcytosis and phosphorylation (mention of two specific
processes)
•
Hypothesis: “AQP2 follows a complex intracellular, transcytotic
trafficking itinerary that is regulated at key decision checkpoints
by phosphorylation and cytoskeletal interactions” (use of
intriguing but understandable jargon)
•
1A) Identify the intracellular site of AQP2 phosphorylation: using
AQP2 blocked at the plasma membrane, in endosomes or in the
recycling compartment by mutation, temperature blocks,
pharmacological inhibitors, and mutated accessory protein
expression. (what we will do, and how we will do it)
Dennis Brown, PhD, 2016
Three (independent) Aims
•
AIM 1: Define the intracellular pathways and signaling events that
regulate intracellular trafficking of AQP2 based on new data on
transcytosis and phosphorylation (basic cell biology)
•
AIM 2: Discover the mechanism by which EGFR inhibition
activates AQP2 membrane accumulation and increases urine
concentrating ability (informed basic and translational study)
•
AIM 3: Perform high throughput screening to identify new
compounds that result in VP independent AQP2 membrane
accumulation (unbiased screening - forward looking discovery
aim, but as part of overall research program)
Dennis Brown, PhD, 2016
Final sentence (after listing aims)
Our overall goal is to design novel therapies to
treat water balance disorders, including NDI and
hyponatremia, using a combination of directed
and discovery approaches that bypass the VP/V2R
signaling cascade to modulate cell surface
expression of aquaporin 2.
(reiteration of goals, approach, rationale and
expected outcome – help the reviewer!! Don’t
make it hard work)
Dennis Brown, PhD, 2016
Final (important) thought
I try to write the SA page first
But modify, modify modify as the rest of the
application progresses.
You have only one chance to
make a first impression
Dennis Brown, PhD, 2016