What are you working on?

Using the tools and principles of chemistry, we develop enabling technologies that help biologists understand cell signaling. For example, the dream of every biologist would be to take any particular molecule of interest inside a cell––it could be one protein out of the 20,000 different proteins that are present––and examine its behavior during all types of different processes. These processes include but are not limited to cell division, the process by which a cell becomes cancerous, the process of cell death, and the process of
differentiation. If we could essentially make a movie of this, with angstrom resolution and in real time, we could actually fi gure out how the protein functions, behaves, interacts with its neighbors, and moves around within the cell. Unfortunately, this is currently impossible. But in the big picture, we’re trying to develop technologies that will make it possible. We’re making methodologies that allow us to take various chemical probes, which are capable of reading out specifi c types of information about proteins, and target them to any
specific molecule we’re interested in learning about. So it’s a chemical problem, but it has biological applications.

Could you mention a specific example?

When I’m telling non-scientists about the work we do, I typically show a movie. The nice thing about our research is that it’s very visual. Let me give you a specific example. ABL is a protein, and when there is a mutation that causes the behavior to become irregular, a particular cancer called chronic myelogenous leukemia can arise. A recent drug, which is very successful at curing this particular form of cancer, is called Gleevec. It is sold by Novartis and it is one of the most successful examples of drug design. Its molecular
target inside the patient is this protein called ABL. Because it is such an important drug target and is a link to this particular type of cancer, everyone would like to know what it does. What are its biological functions? How does it behave in a cell? Now, in traditional cell biology, the most common way to study proteins is to take, say, a million cells, kill them, and then extract and study the purifi ed protein of interest in a test tube. But when you study a protein in its purifi ed form, you’re losing a tremendous amount of information due to the fact that it’s no longer in its natural context. You‘re losing information about how it’s traffi cking inside the cell, you’re losing information about how it’s being regulated by different cellular components, and you’re losing single cell information because you’re averaging across a large and heterogeneous population. So we developed a way to visualize, in a single live cell, exactly when ABL is activated. We can do this because it’s
an enzyme that shuttles between the active and the inactive form. Being able to visualize when it’s on, when it’s off, and where that happens, provides much more information than the traditional cell biological techniques.

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