Writing a Grant: Significance and Innovation

The significance and innovation section is a place for you to showcase WHY the work should be done – WHY there is a significant need for your study, and HOW the work is different from everyone else’s approach. What makes it groundbreaking, original research, work that will advance our scientific knowledge?

Significance

Let’s start with significance. Depending upon the government agency and/or institution to which you are applying, you will need to tailor this section to highlight an unmet need specific to the goals of the organization or funding opportunity to which you are applying. Whether you’ve identified a novel target for the treatment of a rare disease or you’ve designed technology with applications pertinent to national defense systems, you’ll need to be specific about what the problem is, the extent of the burden, and the paucity of adequate solutions to address it. 

As an example, let’s assume that you’ve uncovered the previously-unknown role of a kinase in neuronal death and loss of motor control. A well-structured significance section may have the following subheadings and content:

1. Nature of the disease and current unmet need

   • What is the underlying cause of the disease?

   • How many patients are affected in the U.S. and worldwide?

   • What is the total economic impact?

   • What is the clinical presentation of the disease?

   • How is it treated, and what gaps in the standard of care have been revealed?
     

2. Target Identification and Validation

   1. Are there mutations in the kinase that direct correlate with disease?

   2. Has overexpression been shown to increase neuronal death in culture? Conversely, has knockdown been shown to be protective?

   3. What is the phenotype of the knockout mouse? Do these animals present with improved mobility? Do they have increased survival?

   4. Is the target druggable? If so, are there tool compounds available that could be assessed pre-clinically?

Innovation

With this foundation firmly established, you now can build the framework for how your proposal approaches the problem in a way that nobody else has tried. How will your approach change the way that people think about the problem? For some, composing this section of the grant may be foreign territory and lead to countless blank stares at the laptop screen. When you get lost, remember that there are several types of innovation. In his first book, Mapping Innovation: A Playbook for Navigating a Disruptive Age (McGraw Hill Education, 2017), Greg Satell outlines four categories in what he terms the “innovation matrix”:

Adapted from: Mapping Innovation: A Playbook for Navigating a Disruptive Age

The problem, as addressed in the significance section, is the need being satisfied by your research. The domain is the set of skills required to solve the problem. Let’s look at our kinase example to highlight the utility of this matrix. As part of your pre-clinical animal studies, you’ve determined the efficacy of a tool compound known to inhibit the kinase. The molecule dose-dependently reduces neuronal death and motor dysfunction, but it’s also poorly absorbed and leads to weight loss in rodents. The only means of improving the drug-like properties is to develop a novel chemical synthesis pathway. In this case, the problem is clear, but the set of skills required is not. Thus, you’re on the verge of breakthrough innovation. 

Obviously, this matrix is generic, but it can help to put your research into context. Keep in mind that the more specific you are in defining the problem, the more distinctly you can describe your innovative solution. Furthermore, no solution is complete without a few descriptive figures and a schematic of goals and objectives. Not only do you want to show that you’ve solved a certain need, but you also want to demonstrate feasibility, intermediate milestones, and future efforts. 

Lastly – and this point can’t be overstated – be sure to circulate your significance and innovation sections to as many of your mentors and peers as possible. If it’s not clear to them, it certainly won’t be to your reviewers!

Next up…attacking the Approach!  

Note: The National Institute of Allergy and Infectious Diseases provides sample applications along with corresponding summary statements.