hi girls my name is sue yanga and I am
currently at the MIT Koch Institute
which is a building
our 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
oh thank you for cancer is surgical
debulking which is basically removing of
the mass 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 to be the most to in order to do
the most effective therapy and so cancer
cells are basically cells that have
unusual dividing ability 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 in the
surface in the cell in order to find and
then tell locate where the tumors are
and tell the surgeons okay this is the
place where I should remove the
biological tissue and you don't want to
damage the healthy tissue around it so
you want to be very precise and very 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 the
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 both so we can talk
about both of them today so the
biological martes goal 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 sends its in
DNA takes over the local mechanism of
the bacteria and begins to replicate
itself
so what we can do is hack the 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
you're not up 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
choose 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 ourselves 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 graphite
is what you find in your pencils in
ledge and so it has very interesting
optical and electrical properties it's
very well studied but for us what's
interesting about it is the wavelength
at which it's light this is in the
second window near-infrared wavelengths
and so it's slightly longer than the
visible wavelength and the cool thing
about this is it's able to penetrate
deep 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 was going
to light up and tell us oh this is where
we should go ahead and remove
bath so the first model that we have
actually done in our lab is on ovarian
tumor and ovarian tumor is one of the
tumor bottles that is very difficult to
detect early on it's unlike you know
things like breast tumor you can't feel
it and when usually when the surgeon or
the doctor diagnoses it's quite late in
the stage of the tumor so it could have
turned a metastatic and metastatic means
that the tumor cells have detached from
the body and travel to other parts of
the body and so proliferated other
tumors throughout the body so this is a
stage do you don't want to reach so
it'll be very cool if you can put our
probes into mice with ovarian tumor
light up the tumors give the surgeon
damaged and the church and can go ahead
and move the tumors in the myself and
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
of lit up so we have injected the mice
with trillions of a 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 but 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 my eye but
because he has the imager he can go
ahead and move 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 doctor nos at
from mgh he's doing surgery on mice and
you can see on the screen you can see
brightly lit up this is where the tumors
are and this is where I should take them
and so here's a serial image of what's
happening so here's the
probst lighting up where the tumors are
this is what happens when the surgeon
goes in by I and is like okay 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
term which 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 sage two different
geometries so I call this in your age in
your 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 and a tendency to stick
to the walls and tumble around but if we
can change the state 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've looked at
varying tumor and now I 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
passed through are very specific and
very small so it's very hard to deliver
from your bloodstream very strug the
imaging agents to the actual brain mass
so what we have done here is actually
engineered the head peptide so the
proteins at the head of our age so that
it allows for travel across the
blood-brain barrier so we can deliver
these imaging molecules to tumors in the
brain so one thing to remember here is
that the scale that we're working at the
scale at which we're working it's very
very small so if you look at CNT or the
hour phage really it's about
times a hundred thousand times smaller
than a strand of your hair so there's
really really tiny face so when I make
the small phage they're even smaller
than our regular phage a regular phage
is about 800 nanometers so here's an
example of 289 a meter 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 images 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 you
know 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 protein so that means
big glow and if we send in our fade 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 page and in the red
spread around the nucleus in the golgi
region is our phage so just tells us we
can possibly deliver things to inside
the cells of the cancer so that means we
can 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 we can
remove them effectively but we can also
locally care 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 netlab and the
two things that I've done is you know
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 isn't
possible with that a collaboration that
happens between the colleagues I have at
the MIT Koch Institute as well as the
scientists we have at the Lincoln labs
so that's another really cool thing but
others projects it's so very broad and
so it brings in so many different
techniques and brings in so many
different people as I really want to
thank them and another aspect of this
work that I really find meaningful is
that it's but I am personally funded by
families that are affected by these
types of tumors on these types of
diseases and so I really want to thank
the the Goodwin cracked our staller and
salmon families who have been really
generous with their funding for this
project and yeah finally I want to say
that for me the m13 is kind of a
building block we're here all as girls
who built and so for me for my building
projects is 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 yeah thank
you very much for listening please feel
free to ask me any questions I can talk
more about myself or I can talk mark my
research I yes thank you
yes samples from cancer but these detect
intact cancer or is it just Civic it can
detect any type of cancer as long as you
have a specific differentiating markers
on the cancer that you know of yeah so
not only is this use foreign 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 so then you
can do that which makes it a very
elegant very cool molecule which is why
I think it's you know something i should
be using
you