Novel Proteins to Fight Superbug Bacterial Infections


Hi there, everyone. We are team Lyseia, and
we are so incredibly excited to share
with you the results of our work over the
past couple of years now. Kind of a funny story
as to how we all got together, it was
the very first day of our biochemistry class
and our professor went to the front of the
room and he said, if you’re interested
in entrepreneurship and biotechnology
send me an email. Of course, who could
turn that down? So all of us ended up
sending him an email, and we ended up joining what
is now known as the Chem-H Entrepreneurship Club. And without having
known each other before, I think we kind of got
lucky to have been placed on the same team together. Not only do our
personalities fit quite well, but we also have a diverse
array of academic backgrounds that we come from. So I’m Zach Rosenthal. I’ll be graduating
from Stanford tomorrow with a degree in chemistry. I’m Christian. I’ll also be graduating
tomorrow with a degree in chemical engineering
and electrical engineering. And I’m Maria. I graduated a year ago with
a degree in bioengineering, and I’m currently pursuing
an MD PhD at Stanford. Thanks, guys. So we’ve been working on this
project for almost two years now at Stanford,
and we’re really excited to update everyone
as to how far we’ve come. The problem of
antibiotic resistance– and of multi-drug resistant
organisms in particular– is already in issue. In 2013, there were two
million illnesses along with the corresponding
23,000 deaths. But what’s even
more astonishing is how this problem is expected
to exponentially become a bigger deal. By 2050, there’s expected to
be a global economic costs of $100 trillion along with
10 million deaths per year. In fact, the number
of individuals that will die from multi-drug
antibiotic resistant organisms is expected to be larger than
the number of individuals who die from cancer. And what’s even
more astonishing is no major pharmaceutical
company seems to be viewing this as
an issue worth concern, with only seven drugs
currently in any advanced form of clinical trial. The problem has become so large
that the director of the CDC has described this as
a nightmare scenario. And so now, we will tell you
what our proposed solution is. Our solution is to use
engineered bacteriophage endolysins. Endolysins or lysins, are
proteins used by bacteriophages to break out a bacteria. We have identified several
lysins with broad activity, and we have engineered them
to improve their efficacy against gram-negative,
multi-drug resistant bacteria. Compared to traditional
small molecule antibiotics, lysins show more promise
because resistance development is very little to none. The way our protein
works is that it first penetrates the outer membrane
of the gram-negative bacteria, and then it breaks down
the peptidoglycan layer. And due to the high
internal osmotic pressure of the bacteria, leads to
cell lysis and cell death. After pitching our
idea at Stanford, we got seed funding from
Stanford Chem-H, an institute with Stanford, to do a set
of [INAUDIBLE] experiments. With the money, we were
able to express and purify our protein for testing. As you can see, in this plate,
we did not add any antibiotic. And in this middle play,
we added our protein. And on the right we added
kanamycin a known antibiotic. From these results, you can
see that our protein has the same capacity as kanamycin
to kill a gram-negative model E. coli. And with these
positive results, we’re going to scale up our
production of protein and send them to a contracted
research organization to test against the pathogens
that we’re really interested in. Along this way, we
never really expected to go from slides to
actual experiments, and we learned a lot
of valuable insights that Maria will explain. So the first takeaway that
I want to share with you all is that it’s OK to
buck the status quo. So in the
pharmaceutical industry, when you’re looking
at developing drugs, a lot of people think that
if you are just an undergrad you don’t have
much to contribute. I mean, you guys are
as high school students and look what you’ve
already contributed. So don’t be afraid to
go out there and say, I have a skill set
and I can do this, even though people
think that I might need a PhD or advanced degree. Because there’s so many issues
in the pharmaceutical space that needs to be addressed,
and anyone at a basic research institute who has access to a
wet lab can make huge strides. So don’t forget that you
have the power to do that. Don’t be afraid to be naive. None of us knew anything at
all about multi-drug resistant bacterial organisms
before joining this club. It’s even a mouthful to say. But I think that maybe one
of our biggest strengths when first approaching
this problem was the fact that we were naive. We were able to
broadly look at all of the available options that
were currently being pursued around the country, and without
any preconceived notions as to what would be
a good or bad idea, we were able to come
to our own conclusions, combine different approaches,
and ultimately settle upon our proposed therapeutic. You should also reach
out and reach up. When we first
started the project, we reached out to a lot of
industry experts and professors both within Stanford
and outside. And sometimes it was
daunting, because we felt like they wouldn’t
be interested in talking to us about our idea and
seeing what they thought of. But in fact, many of
them have reached back and have gave us invaluable
insights on the way they think our products should
have gone and the way they think that our product is. Related to that is that you
want to get as much advice as possible, but at the end of
the day you and your team have to make your own decisions. So when we were working
on this project, we met with a bunch of
professors, physicians, people in local biopharma
companies, and a lot of them are encouraging
and gave us advice. And some of them said,
this will never work, stop wasting your
time, don’t do this. And people might say
things like that to you. Some of your projects
might seem impossible, but we’re engineers, and we
make the impossible possible. So don’t let a few
naysayers get you down. Take all their advice– maybe
they have good criticisms– and find a way to
address them, but still stay true to what you
and your team want to do. So this point is
really important to me. I think sometimes
in our society, there’s this false
dichotomy where you can either start a company
or pursue higher education. So you could drop out
and have a startup. A lot of my friends at
Stanford, for example, dropped out and did startups. And I think that you can
do that if you want to, but we all have seen
the value of continuing into higher education. So Zach’s going on to get an MD. Christian’s getting a PhD. I couldn’t decide,
so I’m getting both. And you can do that and
still have a company and still make a difference. So don’t think that you can
either be an entrepreneur or go on to be a
scientist or a doctor. You can do both. And I think, we all think,
that you could actually be a better inventor by
getting more education. So you don’t have to say no
to your educational goals to pursue your research and
your entrepreneurship goals. And the last point I want
to make, is share your work. So you might think that your
products are early stage, you’re not done yet, you do
want to show it off to the world because you might notice that
it’s an unfinished prototype. I wouldn’t worry
too much about that. We shared our work
really early, and because of an article that was
published in just an on campus publication– an NPR correspondent
had come to Stanford and needed to cover a science
story, and he saw that article and he was like, oh
OK, I’ll go come talk to these young inventors. And that ended up getting us a
lot of new press, new funding opportunities. So don’t be afraid to
put yourself out there. Usually press can
only be helpful, and it can not only get you more
funding and more opportunities, but it can inspire other people
your age to pursue inventions. Because when I was
in high school, I had no idea that
I could do the stuff that you guys were doing today. So even by showing other
people that they can do that, you’re doing what you can to
push other students forward. So share your work. We wouldn’t be
standing here today without the help of the people
who really made this possible from the beginning. So at Stanford, we
were lucky enough to be mentored by a chemical
engineering professor– Chaitan Khosla– who’s had
out back from the beginning and helped us with
the initial funding. We also had industry mentors– so from both biotech
and investment banking– who have had our backs and
showed us how things work in the quote unquote real world
outside of the university. And lastly, we do
all of our research at the Macromolecular
Structural Knowledge Center, which is a lab space on campus. And so Mark and Daniel are
there, boots on the ground everyday, helping us to
express and test our proteins. And lastly of course, I’d
love to thank the Lemels N-MIT foundation for bringing
us here, for the funding, and perhaps most importantly
for letting us interact with you guys. Because you are going to
be standing here one day, and I can’t wait to see that. Thank you. We have about a
minute and a half if anyone has a
question for the team. Way up in the back? The possibility that these
bacteria could evolve to resist the
protein you created, and how do you
propose handling that? Sure, so people have done
experiments with lysins, and the reason we think they’re
so good at not developing resistance is that you
can culture bacteria for a bunch of generations, and
see if they develop resistance. And with standard
antibiotics, you typically develop resistance very readily. But when people have
tested other lysins, you don’t see development
in 50 generations, so we’re hoping that
our technology will work in a similar manner. Are there other questions? Yeah, so what’s patentable
about your invention, and who’s going to own it? Yeah, so we hope to
own it initially. We want to incorporate
and use our startup to get it through some
of the initial stages. And what’s patentable is
that we’re using protein engineering techniques
that are somewhat novel, as well starting from starting
material that’s novel. So we’ll probably go
after a composition of matter patent over the
final form of the protein that we’re going forward with. Thank you, guys. We’re going to move
on to [INAUDIBLE].. [APPLAUSE]

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