NINDS's Building Up the Nerve

Episode 3: Initiating the Research Idea

NINDS Season 1 Episode 3

Hear from program directors Drs. Glenn Nuckolls, Francesca Bosetti, and Shai Silberberg on choosing a research topic, reading a funding opportunity announcement, and talking to your program director.

Building Up the Nerve is a podcast from the National Institute of Neurological Disorders and Stroke for neuroscience trainees that takes you through the life cycle of a grant from idea to award at NINDS with the people who make it happen. We know that applying for NIH funding can be daunting, but we’re here to help—it’s our job!

Related Resources:
https://projectreporter.nih.gov/reporter_matchmaker.cfm?source=RPCO&new=1

Transcript: http://ninds.buzzsprout.com/558574/2050863-episode-3-initiating-the-research-idea

Lauren Ullrich:

Welcome to the National Institute of Neurological Disorders and Stroke's Building Up The Nerve, a podcast for neuroscience trainees that takes you through the life cycle of a grant from idea to award at NINDS with the people who make it happen. We know that applying for NIH funding can be daunting, but we're here to help. It's our job. Hi, I'm Lauren Ullrich, a scientific program manager at NINDS, and we actually have a guest host today.

Michelle J-L:

And I'm Michelle Jones-London, the Chief of the Office of Programs to Enhance Neuroscience Workforce Diversity here at NINDS. And we're your hosts today! Last time we gave a big picture overview of the grant cycle and what to expect for the rest of this podcast. On this episode, we are going to do a deeper dive, beginning with initiating a research idea. We are going to talk about choosing a research topic, different types of grant mechanisms, how to read an FOA, and where to find the resources to actually help you submit a successful response to the FOA. As always, I want to state the disclaimer that everything we talk about may only be relevant for NINDS and if you're applying to a different NIH institute, it's always best to check with them about their policies.

Lauren Ullrich:

Okay, so joining us this episode are Dr. Francesca Bossetti, a program director in the neural environment cluster, Dr. Glenn Nuckolls, a program director in the neurogenetics cluster and Dr. Shai Silberberg, who does double duty as director of the Office of Research Quality and a program director in the Channel Synapses and Circuits cluster. So let's begin with introductions. Francesca, do you want to start us off?

Francesca B.:

So, thanks for having me here. Uh, at NINDS, I oversee, the ischemic stroke research portfolio as well as the blood brain barrier research portfolio. I've been here for nine years. And before I was principal investigator in the intramural research program at the National Institute of Aging at NIH studying n euroinflammation and also models of Alzheimer's disease, aging and demyelination. U m, some of my hobbies outside of work: volleyball, I've been playing since I was in high school and I never stopped and it's really fun. And, u h, recently I took on karate as well.

Lauren Ullrich:

Nice! Glen?

Glen Nuckolls:

Okay. Hi, I'm Glen Nuckolls. I'm a program director in the neurogenetics cluster and I manage a portfolio of grants in the muscular dystrophies, spinal muscular atrophy and peripheral neuropathies. Um, so I also, uh, I'm the designated federal official for a committee called the muscular dystrophy coordinating committee and involves NIH and other federal agencies and advocacy groups. And, uh, we meet to talk about issues of importance to the stakeholders in the muscular dystrophy field. Uh, so I've been at NINDS for five years, uh, in this current program director position. Before that, uh, I worked for a different Institute, the National Institute of Arthritis and Musculoskeletal and Skin Diseases for 19 years. So I started in the intramural program doing cartilage biology and skeletal development. And then I was a review officer, scientific review officer. And then for 10 years, I was a program director for, uh, muscular dystrophies and muscle diseases. And I also did a brief period as an acting division director for extramural activities. So hobbies, so I'm learning how to weld steel, um, uh, uh, shielded metal arc welding, which is also known as stick welding for kind of some practical purposes and some, you know, attempts at art, so.

Lauren Ullrich:

That's exciting. Shai?

Shai Silberberg:

Hello. Uh, my name is Shai Silberberg. I'm the director for research quality at NINDS and also a program director. And, uh, my focus as a program director is on, uh, basic research on ion channels and transporters. As the director for research quality, I, uh, oversee activities at NINDS, uh, related to improving the quality of science. I'm also involved in many, uh, external activities, uh, in NIH in general and also internationally to try to improve the quality of science. Been here now for, uh, 15 years. And, uh, before coming to NIH, I, uh, was a associate professor at a university in Israel, uh, studying, uh, the physiology and biophysics of ion channels. When I came to NIH, I was first in the intramural program for three years doing research and then moved over to extramural. As hobbies, I don't have a lot of time for hobbies, but, uh, I enjoy sailing, uh, and photography.

Lauren Ullrich:

Nice.

Michelle J-L:

So a lot of wisdom around this room and also just interesting people. So hopefully this gets you, it gives you a sense of the knowledge base that we have, um, at the NINDS but also that we're people too.

Lauren Ullrich:

Yeah.

Speaker 6:

[music playing in background]

Michelle J-L:

So to dive in, we said we would talk about how do you think about developing a research question. So let's start with the research question itself. At a lot of meetings, what I'll get is misconceptions about the kinds of research that NIH will fund. And what I'll hear is that"NIH only cares about translational research" or"NIH only wants disease focused research." If an applicant's research is purely basic science, can they still get funded from NIH?

Shai Silberberg:

Oh, absolutely. As a program director in a very basic, uh, portfolio, uh, it's important to recognize that the mission of NIH and of NINDS is to acquire knowledge, uh, that can hopefully then be used to improve the well being of, of people. So basic research is, is of fundamental importance and actually at NINDS, we specifically have a program to encourage, uh, grant applications and basic research.

Lauren Ullrich:

So if an applicant has a basic science question that could span multiple institutes, how do they know which one to apply to?

Francesca B.:

Well, they can start to reaching out to, to a program staff in one of the institutes and uh, uh, hopefully, um, they will get an answer or they could, uh, engage with multiple, uh, institutes and see which one, uh, is the most appropriate for, for that proposed research.

Glen Nuckolls:

Yeah, um, NIH also has a website called matchmaker and if you just Google search"NIH matchmaker" uh, it'll take you to it. So it gives you a box where you can put your text from, you know, your specific aims or something like that and it'll match it up with currently funded grants and also identify program directors that have that, that area. So, um, you know, please contact the program director if you need guidance. But, uh, you know, one, one bit of advice is, um, try not to spam us. Uh, it's better if you contact one program director and hopefully that person will respond quickly. And if not, then go on to another program director rather than send it at once to a whole bunch of different program directors.

Michelle J-L:

Yeah. And that sort of gets to: when I contact a program director or a program officer, what things should I ask or shouldn't I ask in terms of the grant process when I reach out?

Francesca B.:

So things to ask are, first of all, if you engage in the discussion with the program director, it would be good to have at least a draft of the aims of the project that you are interested in moving forward. And uh, and then you can ask if that is mission relevant for the Institute. And, uh, you can ask, uh, you know, for general comments about, um, what is the, um, what is an appropriate study section to review that application or if there are any things that, uh, could be a problem, could be problematic as written, but you shouldn't ask us to help you write the proposal or, um, you know, you shouldn't, uh, ask us to make the decision for you whether you should keep one experiment in or not. These are things that are, uh, best discussed with your mentor and colleagues.

Shai Silberberg:

I, if I may add to that, I think an important thing to do is to reach out early, not to have your grant fully written, three days before the submission date and then say, you know, can you give me advice? That's way too late. Spend a lot of time putting together the ideas of specific aims and where you see this project going. And that's a good time to get advice. And only after you get advice from program staff or mentors, from colleagues, that's the time to start writing the application.

Glen Nuckolls:

Yeah. And I think particularly in the, uh, in the F and K awards, there's a lot of intricacies to those, uh, mechanisms. And so contacting us early, a lot of the features of those types of grants are different with different institutes. Uh, so it's good, you know, to check with the program director and make sure that you're applying to an Institute that accepts, you know, that funding opportunity. Yeah, I agree, way in advance.

Lauren Ullrich:

So speaking of specific aims, I think there's a lot of strongly held opinions about how aims should be structured. And sometimes trainees can get confused or, or think there's a right answer. And so I was wondering if you had any advice about how to approach the aims section.

Francesca B.:

So I can start by saying that the aims should make a story so they should be tied to each other, but they should not depend on each other and specifically don't want one aim to be dependent on the success of the previous aim because that is a big issue that always comes up in review. So independent but tied scientifically.

Glen Nuckolls:

Yeah, I think that, you know, most draft aims that we see are overly ambitious, uh, from, from new investigators and also from senior investigators. It's just that new investigators are even more overly ambitious. Uh, and uh, reviewers like to see a manageable set of aims that are done in depth. So I think, uh, you know, the depth of understanding that will be gained from it is much more important than the breadth.

Michelle J-L:

I think that's a great point. And I think it also ties in to, especially for fellowships and career development awards, you have a specific timeline for the training. And so if the research plan doesn't match the actual time available for the training, it's a disconnect and it's going to raise a flag. Speaking about specific aims, Shai, do you want to talk a little bit about, um, NIH is, it's always been a priority, but now we actually put it out in front and in the review criteria. Do you want to touch a little bit on rigor as the head of the office here at NINDS?

Shai Silberberg:

Sure. I'll be happy to. It's important to recognize that what I'm going to talk about has been implemented primarily for R01s and other advanced, uh, forms of funding. For fellowships. NIH has not yet come out with specific guidelines. However, these should be kept in mind when, when putting the application together because they relate to doing, you know, high quality and good science. So NIH introduced four, uh, enhancements to, uh, the grant review, the first one being the rigor of the prior research. In other words, when you put in an application, you need to, uh, consider whether the data that you're using to make the point why you want to do what you want to do is actually done carefully. And if there are issues with some of that data, how you going to address them within your application. So it's not dead in the water if one of the pieces of information you using from other, either your research or someone else's research has potential issues in it because you can see how you will address it when, you know, when you come to do your own experiments. The second thing is you have to describe what you're going to do in your application to minimize unconscious biases. So, you have to describe the rigor of the proposed experiments, right? And, uh, that's important. So for example, issues such as, you know, can you blind the experiments and to minimize, uh, biases associated with that. Can you randomize your samples when you do the experiments, how you come up with the sample size? These are all important issues that should be discussed if, if, uh, if at all possible. The third, uh, addition that was made was authentication of key biological variables. Uh, it's known for example, that up to 30% of cell lines are misidentified. So you might be thinking that you using one cell line, but in actual fact you're, you're using a very different one and you have to describe what are you going to do to, to make sure that your cell lines are what they, you claim they are, that the antibodies are actually specific and work well and so on. The fourth addition is biological variables such as sex. And I'm emphasizing here such as sex because there are many other biological variables that need to be taken into consideration. So for example, if, let's say you're studying stroke and you're going to use animal models, it maybe doesn't make a lot of sense to use young healthy animals as your model as opposed to aged animals that perhaps have hypertension. It's important to consider which variables would be important for the experiments that you propose to do.

Lauren Ullrich:

Okay. I'm gonna shift gears a little bit. And, um, so this podcast is mostly aimed at trainees and a lot of times we get questions about, what should the relationship be between the trainee's project and the mentors project. So there can't be overlap, but how similar can it be or how different can it be? What are the things to think about when coming up with a project?

Glen Nuckolls:

Well, you know, first of all, um, training awards usually don't contain enough funds to pay for the entire project. So there's kind of an assumption that the mentor, you know, has a grant or has support to make sure that the project gets done to pay for a lot of the resources for it. So, you know, that kind of requires that there's a relationship between the research being done through the fellowship and that from the mentors' grant. Um, but I think it's really important for trainees, maybe even before they join a lab, to start a conversation about, you know, what's gonna be my part, how do I intellectually contribute to this? How do I establish a scientific niche for myself? And you know, that conversation should be ongoing throughout the training period. And so certainly when the trainee is working with the mentor to develop a grant application, the trainee should be the intellectual driving force on it. Uh, and it, it should be agreed with the mentor of, you know, uh, if this works out than, than what parts can, uh, can the trainee take with him or her to the next position?

Michelle J-L:

Anything to add Francesca?

Francesca B.:

No, I agree that overlap, just cutting and pasting the mentor's aims is a no-no. And of course you cannot do a totally different thing because otherwise there wouldn't be research funds to support the project, which is tied to the mentors R01 but again, a niche looking at a, you know, still within scope but to something new, it would be the ideal situation.

Lauren Ullrich:

And this is something that a program officer could give you guidance on.

Michelle J-L:

And I think especially for some of the NINDS programs like the NINDS F32, there you really do want to come up with an idea that will have your intellectual ownership. And then more broadly, even for the K99/R00 it's explicit that they talk about what piece of the project you'll take with you for the R00 part.

Glen Nuckolls:

Yeah. I think for K applicants particularly, they need to be thinking about what is that next grant look like?

Francesca B.:

Exactly. Their independent R01. And then you know, instead of approaching their K project, as you know, here's, here's some interesting science and I'm g oing t o see where it takes me. It should be, it's filling the gap in preparation for submission of that R01. And you know, I tell K applicants sometimes here's a great opportunity to, you know, use your mentors money to make the mouse models that you want or create the resources that you want. You know, so a, build yourself a treasure chest in resources that's g oing t o make you successful as an R01.

Shai Silberberg:

If I, if I can add, uh, to the treasure chest: learn to do careful science, learn to do rigorous science and to report everything transparently. You may not find these practices in every lab and in every group that you interact with, but if you adopt them, then your chances of success will be significantly greater because you'll gain the respect of your community.

Michelle J-L:

So we've talked a lot about the research idea, the specific aims, and touched on rigor. I guess another sort of question that we get from people is the opportunities themselves. How do you tell the difference between the different types of the FOAs? For some it looks like alphabet soup. It's RFAs, PAs, PARs, and now we have the NOSI. Um, would you guys take us through what each of those are?

Glen Nuckolls:

Uh, okay. So, uh, program announcements come in different flavors. So, a straight program announcement. Um, so you know, soon that will only be parent announcements will be program announcements. But traditionally it means that, uh, it's identifying a, uh, an area of science, there's no set aside funds, there's no special review. If it's an ROI through a PA, it's going to go to a regular CSR study section. So it used to be that some program announcements were identifying specific scientific areas that institutes wanted to highlight. Uh, and so as I said, they're going away and as Michelle pointed out, they're being replaced by something called a notice of scientific, of special interest or scientific interest, NOSIs. Uh, and so that'll be an uh, um, a notice to the NIH guide that says, you know, this institute considers it a priority to study this area or research. Uh, use, you know, and it'll identify what funding opportunities can be used uh, you know, to, to apply. Sometimes there'll be a set aside of funds. Um, uh, oftentimes there'll be a list of program announcements that, uh, that would be responsive so long as it covers that, you know, uh, described area of research. Okay, so you step up in program announcements, then you get to, um, a PAR. So a PAR, the R part means that it has a special review panel. Uh, and usually that funding opportunity announcement is going to have specialized review criteria that you really need to pay attention to when you write your application. Often times, all of the applications response to that PAR will be reviewed by one review panel. A PAS is a program announcement with a set aside of funds. Means that the Institute has decided its a high enough priority that they want to designate a funding for, um, applications in response to that. And then kind of, um, the top of the pinnacle here is a, is an RFA, a request for application. And so that is, um, can be a single receipt date or it can be multiple receipt dates. Uh, it comes with usually a special review and a set aside of funds and it's the Institute announcing that this is a priority, we want to do, you know, this specialized, uh, mechanism, these special types of grants or this special, uh, area of research. And usually all of the applications in response to the RFA are reviewed together and compared to one another. Some of those announcements, they go through CSR and they'll be percentiled, but usually with RFAs, they're not percentiled. You just get a priority score and a summary statement.

Lauren Ullrich:

Right. So, for example, the F31 is a PA and it's a parent announcement and they all come in, um, sort of together and then they're assigned to different CSR study sections depending on the topic. Um, whereas we have an NINDS-specific F32, that's a PAR because it has special review criteria, and that's reviewed in-house at NINDS and they're reviewed together. And then we have the D-SPAN or the F99/K00, which is an NIH blueprint program. And that's an RFA because it has a set aside budget and very specific scope and specific review criteria. Um, and so the most important thing I think is to read the FOA and see what it says and not to get distracted by what all these little administrative things mean. But it can be helpful I think to, to know what these different letters are signaling.

Michelle J-L:

And especially where it's reviewed. So, for example, it's good to know that for the NINDS, um, the Ks, all of the Ks are reviewed by a review office here at the NINDS and so you don't have to bother about submitting a cover letter on, you know, what study section should this go to? It's really already been decided.

Glen Nuckolls:

So Michelle, if I can add a point to that. Uh, so in I think most--I assume its with the Ks, too, there's form G600, it's an optional form in the application package and it's the PHS assignment form. And you know, that's where normally an investigator can request a specific study section and Institute. Those things I don't think are actually all that important. But what I think really is important is on that form you should describe the appropriate expertise for the reviewers for your application. You don't name anybody unless you want to declare somebody that would be in conflict, but if you describe in as much detail as you want, what's the appropriate expertise, it helps in some cases get it to the right study section and it really helps the review officer get the application into the hands of the right reviewers.

Michelle J-L:

That's a great point, Glen. And I think we can all tell that you used to be a scientific review officer.

All:

[Laughter]

Lauren Ullrich:

All right, so keeping on this FOA topic, many applicants don't really know how to approach the FOA. They just see this wall of text. It seems very intimidating. Um, can you give any on how to read the FOA? What are the important parts to, to really pay attention to and are there any other tips that you have?

Francesca B.:

So I would say the very first thing to look if the title, per se, is of interest, is to look at the eligibility. Because if you are not eligible, there is no point wasting your time and reading all the rest. If you determine that you are eligible, then I would start with the background information, areas of interest, areas that instead, should not be included or are excluded from the FOA. And also pay close attention to the review criteria because those are things that the reviewers will specifically evaluate. So you want to make sure that you have all those points well covered in your application.

Shai Silberberg:

That's very well said. Francesca, I just want to add one thing. One of the very first things to look at is the dates[laughter] because if the dates have passed, then there is no point in reading further.

Lauren Ullrich:

Good point. So finally, do you have any suggestions for where applicants can find resources to help them put their application together?

Francesca B.:

Well, our website has a lot of information about different funding opportunity announcements and uh, and also my suggestion would actually to, to talk with your mentor, to talk with the other colleagues that have been successful and uh, really, uh, try to get a mentoring team that is not just a simply someone who is very familiar with your area of science, but also someone who is very successful in navigating the grant system that can give you very precious advice. And of course you can always reach out to program staff and, uh, we are here to help. But uh, you know, we, uh, it would be much more efficient and effective if you already have done some of the homework.

Michelle J-L:

Yes. It makes a more informed conversation. In our closing of this podcast, what would be your advice for trainees? If you could say one sentence, let's go around starting with Shai. What's your life hack for a grant submission.

Shai Silberberg:

Okay. So my, my recommendation would be that every time you submit a grant application or a manuscript, at least three people are forming an opinion about you. So one needs to put one best foot forward, not to say, okay, I'll let's put it in, I'll see what comments I get and then I'll revise. The best you can possibly do because other people are forming opinions.

Francesca B.:

So if I can follow up on that, I totally agree. But even if you put your best foot forward there is a high chance that you may not get a fundable score. And my suggestion is not to give up. And also that the summary statement with the critique is your best friend and you don't have to take it personally. I know it's hard, when you get it, not to take it personally, but just try to detach you from, from that application and see why the reviewers formed that opinion and what can you do to make sure that doesn't happen again.

Michelle J-L:

Great.

Glen Nuckolls:

So I think for trainees and and new investigators, early stage investigators, um, you know, what you're doing at that point in your career is you're really trying to establish a unique scientific niche and you're developing kind of your own brand. Putting your best foot forward certainly contributes to people thinking the best of you and know that the quality of your product comes through. But I think it's also important, you know, when you're developing your scientific niche that it really is something that you're excited about. And too often, you know, I think people think that they have to put together an application that's completely based on the, the training that they had or something like that. And if it's not really what they're excited about doing, I think that comes through in an application. So pick what you think is the most important science that you can think to do. Sometimes you have to go get additional people to help you with that. You know, still stuff you have to learn about it, but you know, uh, this is what you'll be working on for the rest of your career.

Michelle J-L:

And Lauren, what would you say?

Lauren Ullrich:

I would say take advantage of all of the resources available, especially in the training space. A lot of universities now have programs they have like write your K courses. Reach out to your network and see if other people have applied or to find out about new awards. Just really not trying to do it all by yourself and leaning on that network because they're going to be there for the rest of your career and nobody does science alone. Michelle?

Michelle J-L:

I guess my advice would be to, you know, to sum up what you all said, is to allow yourself time to do all of these things and to be thoughtful and intentional about it. And also realize that the grant at the end, the end of the day, it's not necessarily about the money. It feels like that, but it teaches you a lot about, you know, your long and short term goals. And so it's a valuable exercise to go through, even if at the end of the day you don't end up with the award. I mean, everyone wants that. But even if you don't, I promise you, it will help you focus your passion about the science that you're interested in and it will also force you, especially for these training and career development plans to have some conversations with your mentor or mentor team that maybe you wouldn't otherwise. Um, so I think there's a value in that.

Lauren Ullrich:

Okay, well that's all we have time for today on"Building Up The Nerve". So thank you so much to our guests this week. And also thank you to program director, Dr. Bob Riddle for our theme song and music and we'll see you next time when we tackle the process of preparing the application. You can find past episodes of this podcast and many more grant application resources on the web at ninds.nih.gov

Michelle J-L:

You can also follow us on Twitter at@NINDSDiversity and@NINDSFunding. Email us with questions at NINDSNervePod@nih.gov and make sure you subscribe to"Building Up The Nerve" on Apple Podcasts or wherever you get your podcasts so you don't miss an episode. See you next time.