Bettie Graham: So, the next item on the agenda is a concept
clearance for the novel nucleic acid sequencing technology program.
As many of you know, this has been a program that's been going on for about 15 years.
It was started by Jeff Schloss and it's been very, very successful.
So, Mike is going to present to you today a request to renew this program at the same
level that it's been for couple of times around.
And that's $2 million.
So, Mike?
Michael Smith: So, this is a concept clearance for a novel
nucleic acid sequencing technology development.
This program has been going on -- you could argue that sequencing technology development
has really been a part of the institute for as long as Eric talked about earlier today,
just the kinds of sequencing technology development has changed over the years.
So, we're still very interested in investing in this area.
And today you're going to hear about what are now expired RFAs from a concept clearance
of three years ago; and the awards that we've made, some examples of the kinds of research
that came in under those RFAs; talk to you about a grantee meeting that we hold to help
this community work together well; and then we'll get to the objectives of the concept,
some potential research topics, mechanisms in funding that we're planning on using, and
the timeline with which this will take place.
So, someone intentionally used the word "expired" because the RFA, you know, NIH RFAs have a
life.
They're allowed to be three years long.
That's how long the last set was.
The numbers are indicated here.
So, they're RFA-HG-15, -031, -32, -33, and then -39.
And you can look them up online if you'd like to read them.
I just pulled a few words out of them, and I'm not going to read them to you fully.
Certainly, you can read the slides faster than I will read them to you.
But certainly, a goal to improve quality and efficiency of DNA sequencing, enable direct
RNA sequencing, wanted to read the links, faster turn-around times, et cetera.
And novel chemistries, new physical approaches, instrumentation, and also, again, direct RNA
sequencing.
And really with the idea that we want to push the field forward with an investment in sequencing
-- nucleic acid sequencing technology development.
That's what we were asking for then, and this is a renewal.
So, we're largely planning to do more of the same because I think it's been rather successful.
It also dovetails in well with the strategic planning that you heard about earlier today
from Eric.
So, these are the R01s and R21s that were funded in the first two years of the RFA.
And so, you'll see some protein nanopore work from Gundlach, and also Winston Timp doing
some modified Cs.
There are some solid-state nanopores, Stuart, Shepard.
Wanunu is using zero-mode waveguides to look at picogram amounts of material, which you
start thinking about one cell's worth of DNA in a sense.
Phil Collins has a very interesting method for seeing a polymerase polymerize.
It's different than the way Pat Baio [spelled phonetically] is doing it.
And Tim Buster's also on modified cytosines.
And then the last one is using liquid chromatography and mass spectroscopy to go at RNA sequencing.
A very different approach but reviewed well and we are hopeful.
So, these are the kinds of things that are coming in.
And one of the messages is we've got some nice breadth.
We're investing in places we have invested before, and we're also invested in places
that are possible to work in today.
So, this group does get together.
Jeff ran a technology development meeting for many years.
I inherited that because he retired.
And we ran one last May at Northeastern University.
It was hosted by one of our grantees, Meni Wanunu.
There were 24 grants represented there, which was 100 grantee participants.
And we had the subsequent public meeting, which picked up about another 30 individuals.
What we saw, what we heard was it was -- certainly it was informative and interactive.
It was a good collaboration for catalyst, people got to know each other that hadn't
necessarily met each other before.
We got good, positive feedback.
And you bet we took some lessons learned that we're going to apply to the next meeting.
So, that's one of the ways we're trying to take -- you know, one of the things about
this sequencing technology development RFA is we're really just asking people to come
in with their best ideas.
And then, we're trying to give them some help to do good science, but not direct the science
that they're doing.
So, some of the concept objectives are developing new DNA sequencing technologies, direct RNA
sequencing technologies, and then substantial advances to existing sequencing technology.
Again, I encourage investigators -- this is on the concept side covered by your three-pager,
all right -- encourage investigators to pursue their best ideas and make an accompanying
investment in foundational sequencing technology development.
And it's just worth pointing out that there's talk at times about "solicited" and "unsolicited,"
this actually falls under the solicited category, okay.
Because it's an RFA.
And yet, there's a lot of freedom for investigators to come in with what they think is a great
idea.
And just some examples of the potential research topics, these are very similar to what was
in the last RFAs that I referenced.
Novel chemistries exhaustively sequencing every RNA or DNA molecule in the sample.
Very long reads of 150KB are not sounding so long anymore, but still there's a definite
need for long reads and de novo assembly -- especially perhaps de novo phase disassembly.
Modified bases, direct RNA sequencing without CDNA, and then again orders of magnitude improvement
to existing technologies.
Which sound a little familiar to what the last RFA said.
So, what we've put in the concept clearance is, for R01s and R21s, total of $2 million
per year for three years -- FY19, '20, and '21.
And similar amounts for R43s and R44s which are small business grants, also the same fiscal
years.
So, this is the timeline.
You know, we're currently early in 2018.
And we would expect to accept applications later in 2018, then again in '19, and 2020.
And certainly, that places us very well for, hopefully, another concept clearance, so we
can accept applications in 2021 as the planning process includes a publication.
So, this concept is investigator-focused.
It's foundational for sequencing technology.
It's a continued investment by the institute in nucleic acid sequencing technology development.
And I'd just like to thank a few people.
Melpi Kasapi, really, you know, helped make these slides smooth and did so many other
things.
And many of these slides are pulled from some other presentations we've used internally.
Chris Wellington, likewise.
Carolyn Hutter helped with some good comments.
And I certainly want to point out Ken Nakamura who's done all the reviews for these applications.
And Dan Gilchrist and Mike Pazin really stepped up and helped me during the fall with some
times where I needed some additional help managing this program.
So, happy to take questions or comments.
Female Speaker: Go ahead.
Male Speaker: So, it's a $4 million a year project.
Two for the --
Michael Smith: So, it's $2 million in one fiscal year, and
then that follows out over a number of years.
And then $2 million -- let me go back a little bit.
So, in FY18 we will be making FY19 -- so, in FY19, '20, and '21 we'll invest $2 million
of new money in each of those years.
So, and then that has out year commitments.
Male Speaker: But you said an equivalent amount for the
business awards.
Female Speaker: For the SBIRs.
Michael Smith: For the SBIRs.
Male Speaker: Yeah.
Michael Smith: Yeah.
Yes.
That's correct.
One thing to keep in mind with SBIRs is they tend to not be quite as competitive.
And so, we're going to take what we find there.
Which, based on what we've seen so far, we didn't really get as much as $2 million worth
of activity.
And that's driven by a number of factors like our once-a-year deadline doesn't meet a business's
go-go-go very well.
But the --
Male Speaker: [inaudible] next slide.
Michael Smith: Sorry.
Male Speaker: [inaudible]
Michael Smith: One back.
Male Speaker: Yeah, right there.
Similar amounts -- so, it's a two to $4 million a year project.
Michael Smith: Yeah, it's going to be closer to four in terms
of what the investment is.
But I think, you know, this group is largely focused on the academic side, so that's why
the presentation is largely on the academic side.
Male Speaker: Steve?
Male Speaker: I just want to voice my support for this program,
I think it's incredibly valuable.
And in fact, I would say essential.
And I'd just like to point out that virtually all the sequencing technologies that are on
the market today are disseminated, have their roots in some sort of grant funding where
people actually have to take risks in order to actually try to make something work.
And this is an area that companies are not very good at, at taking risks.
Getting these grants, I think, not only gives some credibility to the approach that an investigator
wants to take, but also involves them within a community that gives them support to advance
the technologies.
And it also gives them validation, as these technologies a require a tremendous amount
of money to actually get to the marketplace.
There needs to be some peer-reviewed process where people that invest money in these things
can see that, you know, this has merit and that there's some validation of that.
And so, for all those reasons I would just really support this program.
And my only question would be whether or not it's enough.
Michael Smith: I would just -- one small thing.
You know, you mentioned that there's a substantial further investment, and I've certainly heard
numbers of 30, $40 million that might be coming in after.
And that's a small -- that's just to get it started.
Male Speaker: [inaudible]
Michael Smith: Yeah.
Male Speaker: [inaudible]
Michael Smith: Right.
Male Speaker: [inaudible]
Male Speaker: Yeah, so I'd just like to echo my support
for this program.
I think it's great, and I think these are the kinds of things that have the potential
to transform the field, and years downfield, that we have no idea, we can't really anticipate.
And again, I think -- like the last two councilmembers commented -- is this really enough?
I mean, are you getting more applications that you could fund deeper given more resources,
or?
Michael Smith: So far, it's been reasonably well matched.
Of course, when you have an amount of $2 million, the interest tends to reflect that, right,
towards the number of applications you get.
Our internal stream processes, I think, leave some room if we got another really good one
to go ahead and fund it.
But there's obviously an internal discussion that squeeze other sides.
Bettie Graham: Yes, Carol?
Carol Bult: Do you have a sense of how many of the people
that attend the group meetings, the grantee meetings, that aren't currently funded by
this program actually go on to submit a grant or are planning on submitting a grant to this
program, sort of bringing in new blood and increasing the pool from which the grants
could be supported?
Michael Smith: So, I think one answer to that is the grantee
meetings are heavily attended by not just the grantees themselves, but also by their
postdocs and graduate students.
It's a, you know, the meeting size is not much smaller -- not much larger than this
room, and so it's very conducive to people actually talking with one another.
There certainly are some cases where what we'll be talking -- so, there are some cases
where grantees are there.
And maybe they're on a no class extension and they will come in for an application later
on.
So, there's a little bit of people who are still in the field, still working on the field.
And there's definitely new people coming in.
If we went back to -- there's an easy way to answer this.
Gundlach's been in for a while.
Stewart's been in for a while.
Meni has been in.
Collins is new.
Shepherd's been there for a while.
Timp is new.
I think Buster was there for a while.
And Zhang is new.
So, was that about a third?
I didn't sit there and count, but.
Carol Bult: So, when you have your meetings, the people
who are currently funded in the program obviously come and bring their postdocs.
But do non-grantees people who aren't involved with any of these groups come?
And is it a way to increase the visibility of the program to get additional people submitting
grants?
Michael Smith: So, the way we structure the meeting -- we're
still moving it around a little bit based on lessons learned.
But the way we're going to run it this year is a little different than last year.
So, this year there's going to be two days of grantee meeting, followed by one day of
an open session meeting.
So, people who want to come in and be involved in the open session with many of the grantees
still around, because we try to make it worth their while to stay, get that opportunity
to learn a little bit more.
And then we have some of the grantees present in the open session meeting because it makes
sense.
Male Speaker: This is back to the budget question.
So, on the slide it looks like, if my rough math prevails, it's about actually 4 million
in --
Michael Smith: It's about 4.5 or 4.4.
Male Speaker: So, this was more than twice the --
Michael Smith: It's two years-worth.
Male Speaker: Oh I -- oh, I see.
So, these are two years at a time?
Michael Smith: Well, it's -- we awarded half these in FY16,
and the other --
[talking simultaneously]
Male Speaker: Thank you.
Got it.
Michael Smith: -- Half in FY17.
And the extra 500,000 or so largely reflects the supplement.
Jay Shendare: So, I'll start by echoing my enthusiasm and
not a ton to add to the comments that Steve and others made.
One thing that I really like about the way that you structure this is really focusing
on niches of sequencing -- not really niches, but aspects like direct RNA sequencing that
haven't really been captured by commercial platforms so far.
And just to something that Carol said, I think from back when I was a part of one of these
awards one thing that was really nice about those meetings -- and the private part of
those meetings -- was that it was a pretty open forum where people could discuss unpublished
results.
I'm not sure if opening it up completely would change the tenor of that, but it might.
But I think that's always a balance with that kind of thing, so.
Bettie Graham: Any other questions?
Comments?
So, I think we will call the vote.
And I'm -- what I would like to say before saying that is that I think staff has heard
that there is enthusiasm for increasing the amount of this program.
But we will vote on the two million that's being requested.
So, could I have a motion?
And a second?
All of those who approve?
Abstentions?
Any no votes?
So, the motion carries.
Thank you.