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The Institute for Molecular Engineering (IME), established in 2011, is a partnership between the University of Chicago and Argonne National Laboratory that explores the intersection of science and engineering. Housed in the glittering new Eckhardt Research Center on the UChicago campus, the IME assembles world-class researchers across a broad range of science and engineering disciplines to translate discoveries in basic physics, chemistry, and biology into new tools to address important societal problems.
Many of those new discoveries have applications in medicine. Matthew Tirrell, PhD, Dean and Founding Pritzker Director of the IME, is a pioneering researcher in the fields of biomolecular engineering and nanotechnology. His team is developing nanoparticles called micelles that can help diagnose cancer and heart disease by binding to tumor cells or dangerous plaques that build up in arteries.
Tirrell will be part of the upcoming UChicago Discovery Series event, "Future Science: Small Scale, Big Impact," that will feature these and more of the game-changing ideas that scientists and engineers at the IME are pioneering. We spoke to him recently about his work impacts medicine, and how the IME is collaborating with physicians and researchers from UChicago Medicine.
UChicagoMed: How do the nanoparticles you're making work in the body?
Matthew Tirrell: The kind of nanoparticles that we make are self-assembled, which means they spontaneously form when you mix the right ingredients. They're spherical, and although it doesn't seem necessary to emphasize the smallness of a nanoparticles, they're about the smallest nanoparticle you can make, down to single nanometers. The reason that's useful is the body has all kinds of filters that it uses to get alien objects out. Smallness is one way of avoiding those kinds of traps.
The nanoparticles we make are also modular, and by that I mean they can easily contain two or three different functional constituents. Some of them can target the disease, some of them can help you image the disease, and some of them can treat the disease in principle. We don't have the total answer how to do everything yet, but these kinds of particles have some particular advantages. For example, the assembly can come apart when it gets to the target, and that can help it get into other places. So that's why we like these nanoparticles.
What's feasible for medical applications of nanoparticles in the near future?
We've done a lot on the targeting side, and we're moving into the diagnostics and therapeutics. Targeting has been easier at first, just because the ability to detect whether something is there is a binary thing-you can either see it or you can't. In heart disease, it's pretty easy to see plaques that build up in arteries already. What's hard, and the element that we add with the nanoparticle, is to determine if they're about to rupture. That you can't tell just by seeing things. But our nanoparticles hone particularly to plaques that are about to rupture. So if you see our particles accumulating in a certain place, it's more than just that there's a plaque there. There's a dangerous plaque there.
What are some other diseases or scenarios where you could use nanoparticles?
There are two basically, and we're working on both of them. One is cancer, and it works the same way as in heart disease, except with cancer we need to think about deploying different therapeutics. The imaging part can be roughly the same though. We're working with James LaBelle in pediatric oncology on micelles that are more effective by making them cleavable when they get to the site, so they can get into cells more easily. Generally speaking, what you're trying to do when you get to a tumor is kill the thing by delivering a drug inside the cell.
The other thing we're working on is a little bit different, and that's to create nanoparticles that stimulate the immune system and create vaccines. So we would create nanoparticles that displayed signals that one might see on the surface of a pathogenic organism, or on the surface of a tumor cell. That way, before either of those things was present, it stimulates an immune response to these things, either to kill cancer cells or pathogens.
In a similar direction, my colleague Jeff Hubbell has created an interesting way of tricking the immune system, not for treating cancer but for autoimmune disease. What he recognized was that we have millions of red blood cells that turn over in our bodies each day. They break into all kinds of fragments and they look weird, but they never provoke an immune response. So there's something about this whole red cell turnover process that tolerates the body against fragments that might otherwise provoke an immune response. So what he's done is develop a targeting approach to direct proteins from pancreatic islet cells, which are killed by the immune system accidentally in the case of type 1 diabetes, to the surfaces of red blood cells. It turns out the tolerance is induced to those proteins, so the body no longer has an autoimmune response to those things.
So this could be used to prevent diabetes from developing?
Right. By the time type 1 is fully evolved, the islet cells are usually shot. But there are screening tests that can reveal a propensity to develop type 1, so if somebody has some of those markers, then a treatment like this could forestall that. It would be something you could give to kids who are at risk, for example.
How do you see future partnerships developing between the IME and the medical side of campus?
I would say that, honestly, the medical school and the Biological Sciences Division have been really excellent partners for us in the early stages. I'm not trying to congratulate ourselves too much yet, because we can only deliver to a certain extent, but people in the medical school have real problems they need to solve, so they're eager to have engineers who don't just want to study their problem, but want to try to contribute something right away. We've had great interactions with John Alverdy in surgery, for example, where we've created polymers that seem to reduce the virulence of bacteria in the gut to reduce infections after surgery. There's really been a tremendously stimulating reception so far from the medical school and BSD, and we intend to keep that going in the future.