UYANGA TSEDEV: So hi, girls.
My name is Uyanga.
And I am currently at the MIT Koch
Institute, which is a building just for cancer research.
And today, I'm going to talk about
the biological engineering that we do in order to find
and image deeply embedded and difficult-to-reach tumors.
So currently in the clinic, the number one therapy method
for cancer is-- thank you-- for cancer
is surgical debulking, which is basically removing of the tumor
masses, and then chemotherapy.
And so it's very important for surgeons
to be able to locate precisely and early
on in the stage of the tumor the masses that they
want to remove in order to do the most effective therapy.
And so cancer cells are basically
cells that have unusual dividing abilities.
So they proliferate without stop.
And they are differentiated from the regular cells around them
by certain markers on the surface of the cell.
And so what we want to do is use these markers on the surface
in the cell in order to find and then locate where
the tumors are, and tell the surgeons,
this is the place where you should
remove the biological tissue.
And you don't want to damage the healthy tissue around it.
So you want to be very precise.
So there are two tools that we use in our lab
in order to find the tumors in the body.
The first is the custom-built imager
that we're working on with collaboration at the Lincoln
Labs, and the second is the biological probe.
It's a little shuttle that we use in order
to go ahead and find the cells in the body.
So we can talk about both of them today.
So the biological marker that we use
is called the M13 bacteriophage.
And bacteriophage really just means bacteria eater.
So it's a virus.
So as with typical viruses, it infects bacteria, [INAUDIBLE]
takes over the local mechanism of the bacteria,
and begins to replicate itself.
So what we can do is hack this system
in order to use this molecule for our own benefits.
It's a very beautiful, very simple sort of molecule.
It's just a piece of DNA-- so a DNA
that codes for its genetic information--
and a bunch of proteins that's wrapped around the body.
And so because we can manipulate the DNA,
we can change the peptides that are on the body of the phage.
And so we can change the protein so that they
have specific binding abilities to certain materials
or certain ligands, or certain markers.
So this is the tumor cell markers that I'm talking about.
We can change the protein at the head of the virus
in order to bind specifically to the surface of a cancer cell.
And we can change the proteins on the body
of the virus to bind to a specific imaging agent
or therapy agent that we can then shuttle
to the surface of our cells.
So for our system here, the imaging agent that we chose
is called a carbon nanotube.
And so a carbon nanotube is just a piece of graphene
that's been rolled up.
And what graphene is is it's just
a single layer of graphite.
And graphite is what you find in your pencils, in lead.
And so it has very interesting optical and electrical
properties, and it's very well-studied.
But for us, what's interesting about
it is the wavelength at which it emits light.
This is in the second window near infrared wavelength.
And so it's slightly longer than the visible wavelength.
And the cool thing about this is it's able to penetrate deeper
into the biological tissue.
And you have less scattering and less interference
from the surrounding materials.
So finally, this is the design of our shuttles
that we send in to find tumor cells.
We have the M13 bacteriophage, which
has a particular protein at the head that
detects the tumor cells.
And we have on the body the CNT, the carbon nanotube,
that is going to light up and tell us
this is where we should go ahead and remove the mass.
So the first model that we have actually done in our lab
is on ovarian tumor.
And ovarian tumor is one of the tumor [INAUDIBLE]
that is very difficult to detect early on.
Unlike things like breast tumor, you can't feel it.
And usually when the surgeon or the doctor diagnoses,
it's quite late in the stage of the tumor.
So it could have turned metastatic.
And metastatic means that the tumor cells
have detached from the body and traveled
to other parts of the body, and so proliferated other tumors
throughout the body.
So this is a stage you don't want to reach.
So it'd be very cool if you can put our probes into mice
with a ovarian tumor, light up the tumors,
give the surgeon the image, and the surgeon can
go ahead and remove the tumors, and the mice will then survive.
So this is a first step in putting our system
to its clinical application.
So this is what happens in real life.
You see here the stomach cavity of the mice.
And in the bright orange, you see all the tumor masses
that have lit up.
So we have injected the mice with trillions
of our tiny little molecular shuttles
that carry our CNT to the location of the tumor.
And using our imager, which we have built with help
from the Lincoln Labs, the surgeon
is able to go in and remove all these nodules.
And the cool thing about the nodules
here is we're getting the ones that are even
below a millimeter in diameter.
So usually, when a surgeon goes in without any guidance,
he might miss these because he's just going by eye.
But because he has the imager, he
can go ahead and remove most of the tumors.
So here's an example of what we're doing in real time.
So during surgery, if the surgeon can directly
refer to the images that he's getting,
then he can go ahead and implement our technology
in a very real way.
So here, we see Dr. [INAUDIBLE] from MGH.
He's doing surgery on mice.
And you can see on the screen, he can see brightly lit up--
this is where the tumors are, and this
is where I should take it out.
And so here's a serial image of what's happening.
So here's the probes lighting up where the tumors are.
This is what happens when the surgeon goes in by eye
and is like, OK, from my experience,
this is where I should take out the tumors.
And you see that there's quite a bit of mass left.
But if we have the imager, then we
have a much cleaner image at the end of the surgery.
And so there's a lot less of a chance
that the tumor is going to recur.
So for me personally, there are two things I'm doing in order
to expand on our system that we have already built.
The first is manipulating the M13 phage
to different geometries.
So I call this inhophage.
Inho just means small in Portuguese.
And so based on the aspect ratio, which basically
is the diameter versus the length of our phage,
they might have very different traveling abilities
in the bloodstream.
So because of their oblong shape,
they have a tendency to stick to the walls and tumble around.
But if we can change this shape to an optimal size,
then there's a chance that they will
travel for a longer period of time in the bloodstream,
and so find the tumors that are farther
from the site of injection.
The second thing is we are expanding on the library
of cancers that we can attack.
So so far, we have looked at ovarian tumor,
and now we want to look at brain tumor.
And the most difficult thing about brain tumor
is the blood-brain barrier.
So it's just a layer of cells that separate your blood
from the matter in your brain.
And the molecules that pass through
are very specific and very small.
So it's very hard to deliver from your bloodstream
various drugs or imaging agents to the actual brain mass.
So what we have done here is actually
engineer the head peptides-- so the proteins
at the head of our phage-- so that it allows for travel
across the blood-brain barrier so it can deliver these imaging
molecules to tumors in the brain.
So one thing to remember here is that the scale at which we're
working is very, very small.
So if you look at CNT or our phage,
really, it's about 100,000 times smaller
than a strand of your hair.
So these are really, really tiny things.
So when I make these small phage,
they're even smaller than our regular phage.
Our regular phage is about 800 nanometers.
So here's an example of 280 nanometer phage, 100 nanometer
phage, and 50 nanometer phage.
So when I make them and I want to look at them,
it's really hard because they're so small.
And you can't just use regular light microscopy
to detect them.
So another interesting thing that I do
is use atomic force microscopy.
I don't know if you've heard of it.
But what it is is basically you take a sample,
and you have this very, very tiny needle
that scans across the surface.
And so you're getting a topology of the surface.
And from that scanning, kind of like reading Braille,
you get a good idea of what the profile of your image is.
So these are the images that I get from this sort of needle
probing.
For the brain tumor, another interesting factor--
not only can we bring the phage to the surface
of the tumor-- so this is tumor here shown in green.
This is tumor that actually has green fluorescent proteins,
so that means they glow.
And if we send in our phage, we see that, oh,
yeah, our phage goes ahead and coats in red the tumor.
But then the other thing we notice
is that the phage is actually internalized into the tumor
cells.
So the phage comes and attaches to the surface,
and then the tumor cells eats the phage.
So in the blue here is the nucleus of a phage.
And in the red spread around the nucleus in the Golgi region
is our phage.
So it just tells us we can possibly deliver things to
inside the cells of the cancer.
So that means we could send in therapies
that disrupt the function, and so in this way,
kill the tumor cells.
And so can we not only detect where they are
and see if it can remove them effectively,
but we can also locally cure them.
So overall, today, we've looked at the very real medical impact
that we can do with imaging and the probe
that we have biologically engineered in our lab.
And the two things that I've done
is look at what we can do to change the geometry,
and what we can do to change the different cancers that we
can attack.
And all of this work, of course, is
impossible without the collaboration that
happens between the colleagues I have at the MIT Koch Institute,
as well as the scientists we have at the Lincoln Labs.
And so that's another really cool thing about this project.
It's so very broad, and so it brings
in so many different techniques and brings
in so many different people.
And so I really want to thank them.
And another aspect of this work that I really find meaningful
is that I am personally funded by families
that are affected by these types of tumors,
these types of diseases.
And so I really want to thank the Goodwin, [INAUDIBLE],
[INAUDIBLE] and [INAUDIBLE] families who have been really
generous with their funding for this project.
And finally, I want to say that for me, the M13 is
kind of a building block.
We're here all as Girls Who Build.
And so for me, for my building project, it's the M13.
And I hope that you guys are able to understand from this
that as an engineer, for me, it's really just
about finding creative ways to use my building blocks to make
a difference, to address the problems that I think
are most important to me.
And so thank you very much for listening.
Please feel free to ask me any questions.
I can talk more about myself, or I can talk more about research.
But yes, thank you.
[APPLAUSE]
PROFESSOR: Any questions for her?
UYANGA TSEDEV: Yes?
AUDIENCE: You were using specific examples
for the cancer, but can these detect any type of cancer,
or is it just specific, or a couple of types?
UYANGA TSEDEV: It can detect any type of cancer
as long as you have a specific differentiating marker
on the cancer that you know of.
So not only is this useful in cancer,
it's also useful in detecting any other material.
As long as you're able to modify the head so
that it is specific to that material or to that cell,
then you can do that, which makes it a very elegant, very
cool molecule, which is why I think it's something
I should be using.
[CHUCKLING]
PROFESSOR: Any other questions?
Great.
Thank you, Uyanga.
[APPLAUSE]
UYANGA TSEDEV: Thank you.
[APPLAUSE]