Professional Documents
Culture Documents
Lynn W. Jelinski, Ph.D. 6406 Hopkins Drive Austin, TX 78734 kc2kg@earthlink.net 843-412-4331
The Statistics
Before the economy tanked: In a good year, about 1/4 to 1/3 of the 70,000 proposals submitted to NIH and NSF, combined, were funded.
http://sciencecareers.sciencemag.org/career_magazine/previous_issues/articles/0490/how_not_to_kill_a_grant_application_part_five_the_fact s_of_the_case_thus_far
A 2011 factoid: NSF received 247 preproposals for the latest round of Science and Technology Centers, 45 were invited for full proposals, 11 were site-visited, and 5 were awarded. Thats a 2% success rate.
http://www.nsf.gov/news/news_summ.jsp?cntn_id=116378
The Statistics
Figure on a 15 20% funding rate. This is hard to accept, because all of us are used to being in the top 5% of our class.
Although many will deny it, dont forget that there is a halo effect.
No matter how brilliant you are, youll need to write lots of applications.
1. 2. 3. 4.
Visit your Foundation, Program Officer, Program Manager Review grants; get on review panels Invite leaders in your field to present seminars at ISU Participate in workshops where the community defines priorities and what will be done next
If you know the material cold, most people can write 5 polished pages a day*.
* A day = 8 12 hours, ABSOLUTELY NO DISTRACTIONS. This doesnt count all the rest of the material (references, budget, budget justification, CV, facilities, support letters)
Allow twice as much time as you think. Dont forget about internal ISU deadlines.
- Put yourself in the reviewers frame of mind. Dont forget that s/he just parachuted in. - Do not confuse the reviewer. - Avoid the smell of blood. - Identify the Alpha Reviewer for revised applications.
You may have spent weeks writing your proposal, but the Average Reviewer is going to spend less than 1.5 hours reading your grant and writing the critique. The Lazy Reviewer might spend less time.
Make it easy for the Average Reviewer to immediately grasp your plan.
noun A dominant dog; a dog that is an alpha male or alpha female. Often used figuratively.
The Alpha Reviewer is the one whose critique is repeated most obviously in the Summary Statement. The Alpha Reviewer will likely be assigned to review your grant again. Pay careful attention BOTH to the Summary Statement and the critique by the Alpha Reviewer in revising your grant.
Why is your approach innovative? How is your approach creative? How are you going to do it?
Examples
STRONG research question What are the molecular mechanisms responsible for the exceptional strength of spider silk? There remains a lot to know about spider silk so we will investigate it.
Stamp-collecting
Examples, continued
STRONG research question Mosquitoes sucked dinosaur blood and then got stuck in resin. Dinosaur DNA, albeit damaged, was trapped and preserved in amber. Can we clone dinosaur DNA?
Examples, continued
Who cares? So what? What happens if you do this?
Silk fibroin has little long-range structure in its liquid state, but assumes an insoluble beta-sheet structure when spun. The theme of insoluble protein formation pertains to diseases such as Alzheimers, Jakob-Kreutzfeld, and Mad Cow.
Bioinspired materials are interesting and related to nanotechnology, which is a field of interest right now.
Examples, continued
Who cares? So what? What happens if you do this?
Silk fibroin has little long-range structure in its liquid state, but assumes an insoluble beta-sheet structure when spun. The theme of insoluble protein formation pertains to diseases such as Alzheimers, Jakob-Kreutzfeld, and Mad Cow.
Bioinspired materials are interesting and related to nanotechnology, which is a field of interest right now.
Examples, continued
Who cares? So what? What happens if you do this? Well create an amusement park with live dinosaurs for the education and entertainment of children. We and our investors will make a lot of money doing so.
Examples, continued
How is your approach creative? How are you going to do it? To measure short-range order and molecular motion in the solid state, we will take advantage of our home-built solid state NMR spectrometer capable of recording spectra under tension.
We will use all the tools at our disposal, including NMR and IR and genetic engineering. Stay focused. No need to throw in the kitchen sink.
Examples, continued
How is your approach creative? How are you going to do it? Well clone dinosaurs. Well fill in the gaps in missing DNA with modern-day avian and reptilian DNA. To be on the safe side, well make all the dinosaurs female and well also make them lysinedependent.
Hypothesis-driven Research
Clear Specific Aims No more than 2 or 3 Specific Aims. Approach small chunks at a time and save the rest for later grant applications.
PUTTING IT ALL TOGETHER: Now We have Answers to the 3 Key Questions, Hypotheses, Specific Aims and an Elevator Conversation
The hardest part of the grant application is already written!
The Abstract and the Specific Aims (or the first two pages) will flow from the 3 key questions. The Elevator Conversation is useful for necessary repetition --- restating goals and significance. Some examples
The first 4 sentences: Sentence 1: What will you do? Sentence 2: Why is it important?
Dont forget that the abstract is hugely important for review panels where members who havent reviewed the proposal vote. Dont simply copy-andpaste the first few sentences from your specific aims section.
Here we seek to understand how structural flexibility and variation in parvoviral capsids control their ability to bind receptors leading to cell infection and also to variation in host range, and also how capsid structures control antibody binding and neutralization. Those areas of study are significant because they are features of all animal and human viruses. While parvovirus capsids appear structurally simple, they are clearly sophisticated biomolecular machines that carry out many functions using variants of a single capsid protein, and the features controlling many functions have now been mapped to specific mutations and capsid structures, presenting an opportunity to gain a complete understanding of how virus-host interactions occur in fine detail. Parvoviruses include the B19 virus, human bocavirus, and Parv4, all of which cause disease in humans. Here we use feline and canine parvoviruses as models to build on our previous studies showing that cell infection and animal host ranges are controlled by specific interactions of the capsids with the transferrin receptors type-1 (TfR) of different hosts. There are also distinct outcomes for viral infection of antibody binding, depending on the binding site and angle of attachment.
Colin Parish, Cornell University, http://funding.niaid.nih.gov/researchfunding/grant/documents/parrishfull.pdf
EVERYTHING should relate to the central question: What are you going to do? Pare away anything else.
It was the best of times, it was the worst of times, it was the age of wisdom, it was the age of foolishness, it was the epoch of belief, it was the epoch of incredulity, it was the season of Light, it was the season of Darkness,
Call me Ishmael.
You need to hook the reviewer in the first few sentences, and certainly by the first two pages.
Specific Aims Microscopy has emerged as one of the most powerful and informative ways to analyze cell-based high-throughput screening (HTS) samples in experiments designed to uncover novel drugs and drug targets. However, many diseases and biological pathways can be better studied in whole animalsparticularly diseases that involve organ systems and multicellular interactions, such as metabolism and infection. The worm Caenorhabditis elegans is a well-established and effective model organism that can be robotically prepared and imaged, but existing image-analysis methods are insufficient for most assays. Priority score: 10 We propose to develop algorithms for the analysis of high-throughput C. elegans images, validating them in three specific experiments to identify Percentile: 2 human infections and genetic regulators of host response to pathogens and fat metabolism. Novel computational tools for automated chemicals to cure image analysis of C. elegans assays will make whole-animal screening possible for a variety of biological questions not approachable by cellbased assays. Building on our expertise in developing image processing and machine learning algorithms for high-throughput screening, and on our established collaborations with leaders in C. elegans research, we will: Aim 1: Develop algorithms for C. elegans viability assays to identify modulators of pathogen infection Challenge: To identify individual worms in thousands of two-dimensional brightfield images of worm populations infected by Microsporidia, and measure viability based on worm body shape (live worms are curvy whereas dead worms are straight). Approach: We will develop algorithms that use a probabilistic shape model of C. elegans learned from examples, enabling segmentation and body shape measurements even when worms touch or cross. Impact: These algorithms will quantify a wide range of phenotypic descriptors detectable in individual worms, including body morphology as well as subtle variations in reporter signal levels. Aim 2: Develop algorithms for C. elegans lipid assays to identify genes that regulate fat metabolism Challenge: To detect worms versus background, despite artifacts from sample preparation, and detect subtle phenotypes of worm populations. Approach: We will improve well edge detection, illumination correction, and detection of artifacts (e.g. bubbles and aggregates of bacteria) and enable image segmentation in highly variable image backgrounds using level-set segmentation. We will also design feature descriptors that can capture worm population phenotypes. Impact: These algorithms will provide detection for a variety of phenotypes in worm populations. They will also improve data quality in other assays, such as those in Aims 1 and 3. Aim 3: Develop algorithms for gene expression pattern assays to identify regulators of the response of the C. elegans host to Staphylococcus aureus infection Challenge: To map each worm to a reference and quantify changes in fluorescence localization patterns. Approach: We will develop worm mapping algorithms and combine them with anatomical maps to extract atlas-based measurements of staining patterns and localization. We will then use machine learning to distinguish morphological phenotypes of interest based on the extracted features. Impact: These algorithms will enable addressing a variety of biological questions by measuring complex morphologies within individual worms. In addition to discovering novel anti-infectives and genes involved in metabolism and pathogen resistance, this work will provide the C. elegans community with (a) a versatile, modular, open-source toolbox of algorithms readily usable by biologists to quantify a wide range of important high-throughput whole-organism assays, (b) a new framework for extracting morphological features from C. elegans populations for quantitative analysis of this organism, and (c) the capability to discover disease-related pathways, chemical probes, and drug targets in high-throughput screens relevant to a variety of diseases. Primary collaborators Gary Ruvkun and Fred Ausubel, MGH/Harvard Medical School: Development, execution, and follow-up of large-scale C. elegans screens probing metabolism and infection. Polina Golland and Tammy Riklin-Raviv, MIT Computer Science and Artificial Intelligence Lab: Illumination/bias correction, modelbased segmentation, and statistical image analysis. Anne Carpenter, Broad Imaging Platform: Software engineering and support.
Carolina Wahlby, Broad Institute http://funding.niaid.nih.gov/researchfunding/grant/documents/wahlbyresplan.pdf
Even for grants that dont require preliminary data (such as NSF CAREER awards), you really need preliminary data.
Style Points Count But Not as Much as the Main Idea and the Research Plan
Dont use too much jargon, too many arconyms, too many abbreviations!
Especially not in the first sentence or two. Reviewers need to keep all these abbreviations in their head, and it makes their task difficult.
Style Points Count But Not as Much as the Main Idea and the Research Plan
Dont overdo the bold and underlines and italics and all three
Style Points Count But Not as Much as the Main Idea and the Research Plan
Double space between paragraphs. The last thing you want is a dense proposal.
Style Points Count But Not as Much as the Main Idea and the Research Plan
Right-justify or not? I say not, as psychobiologists say it is easier to read ragged edge text. This is especially important for NIH applications, where the page margins are 0.5 inch on a side and uneven spacing makes it difficult to read wide expanses of unevenly spaced text. Most RFPs and FOAs are ragged edge. But some think that it looks more professional to use right justification. It probably doesnt matter
Specific Aims and Sub Aims 1.1 1.2 1.3 1.4 1.5 2.1 2.2
Year 1
Year 2
Year 3
Year 4
Year 5
References
Dont bloat your travel budget. Make sure your budget matches your proposal. Seek help from departmental gurus and mavens.
Requesting that an Experienced Senior Colleague Read the Finished Proposal before Submission
A PROVEN key to success, cited in almost every guide on how to write grants.
Its a good idea to provide a list of suggested reviewers. If you know them well enough, simply e-mail them and say: I am preparing a proposal for the such-and-so program at NSF and would like to list you as a potential reviewer. The main idea is insert elevator conversation. Should my proposal be sent to you, I hope you will have time to review it.
Problems with significance: Not significant nor exciting nor new research Lack of compelling rationale Incremental and low impact research Problems with specific aims: Too ambitious, too much work proposed Unfocused aims, unclear goals Limited aims and uncertain future directions Problems with experimental approach: Too much unnecessary experimental detail Not enough detail on approaches, especially untested ones Not enough preliminary data to establish feasibility Feasibility of each aim not shown Little or no expertise with approach Lack of appropriate controls Not directly testing hypothesis Correlative or descriptive data Experiments not directed towards mechanisms No discussion of alternative models or hypotheses No discussion of potential pitfalls No discussion of interpretation of data Problems with investigator: No demonstration of expertise or publications in approaches Low productivity, few recent papers No collaborators recruited or no letters from collaborators Problems with environment: Little demonstration of institutional support Little or no start up package or necessary equipment From: http://www.ninds.nih.gov/funding/grantwriting_mistakes.htm
Fatal Flaws
Insufficient innovativeness, creativity, originality Failure to cite important literature Problems with protections for human subjects: Inadequate protection of identity Unacceptable risks Problems with use of vertebrate animals Annoying the reviewer
1. Answer the 3 Key Questions Answers generate hypothesis Answers generate specific aims Answers generate broader impacts 2. Write Elevator Conversation 3. Write first 2 sentences 4. Write first 2 pages 5. Use the Cauliflower Method to develop the full proposal 6. Use 4-sentence formula to write the abstract 7. Ask a colleague to read it before submission
Sentence 1: What will you do? Sentence 2: Why is it important? Sentence 3: What has already been done? Sentence 4: How are you going to do it and how is your approach special?
Who cares? So what? What happens if you do this? How is your approach creative? How are you going to do it? STRONG research question
Put yourself in the reviewers frame of mind and dont expose your soft underbelly.
The End!