Alexander Jaworski has traveled down his share of paths. He traces the development of his scientific interests from mathematics and physics to biochemistry to the molecular workings of the nervous system. He had also traveled from his native Germany to New York to California before coming to Providence this summer as a new assistant professor of neuroscience.
Jaworski studies sinuous journeys, too. They are shorter and quicker than his own, but they are fiendishly complex nonetheless. His research concerns the surprisingly precise adventures of root-like axons that protrude from neurons to form the connections and establish the circuits that run the body and the brain. He’s trying to figure out how a neuron can extend its axon through a thicket of others to find just the right target.
Jaworski discovered his passion for neuroscience in classes he took while pursuing his master’s degree in biochemistry at Free University of Berlin. He appreciated biochemistry all the more in the context of the nervous system.
“To have that whole spectrum from molecules up to behavior laid out in front of me was really fascinating,” he said. “But because I’m coming from more of a ‘first principles’ background, I didn’t go into behavior, I stuck with the connection between molecules and nervous system function.”
So while some neuroscientists might ponder how neural circuits make us feel reward or pain, Jaworski has a more nuts-and-bolts interest in how those circuits are built. He focuses on the spinal cord and the retina.
Molecules guide neurons
The immediate neighborhood of most neurons is thousands of other neurons of a variety of types. They all emit molecular signaling proteins to form connections, or synapses, with others. Any neuron could be awash in molecular signals meant for others.
Axon guidance, Jaworski has found, is therefore a dynamic process in which a neuron might ignore some signals until a specific condition changes. Then it will act on that previously ignored signal at exactly the right moment to change its axonal trajectory or forge a synapse with another neuron.
“Axons bypass probably a whole number of potential targets they could synapse with,” he said. “There need to be certain changes in the ‘mindset’ of the neuron at any given time. So that’s something I’m interested in: how these transitions are being regulated.”
Not only do neurons appear to change their interpretation of certain signals at different times, but some types of neurons may also interpret a particular signal very differently than other neurons do.
Take for example, a paper Jaworski published in Nature Neuroscience as a postdoctoral scholar at the San Francisco pharmaceutical giant Genentech. He and adviser Marc Tessier-Lavigne were looking at an axonal guidance pathway called “Slit-Robo,” named for the molecule Slit and the receptor Robo that detects it. Scientists had understood Slit-Robo to be a long-range signal between neurons that helped axons avoid inappropriate target areas (e.g., If I make Slit and you have Robo, you’ll stay away). But Jaworski and Tessier-Lavigne reported the case in which certain neurons with Robo would also produce Slit and that somehow this signal compelled their axons to grow together, as if to form a cable.
The many combinations of cells, molecules and contexts allows the diversity of the nervous system to arise from the constraints laid out in DNA.
“You have to specify billions of connections between nerve cells, but you are only working with 20,000 genes so there are many more connections to be specified than there are even molecules encoded in the genome,” he said.
The path to Brown
Jaworski’s formal training in neuroscience, as well as his residency in the United States, began with his doctoral studies at New York University. With adviser Steven Burden, he looked at molecular mechanisms regulating the expression of genes specifically related to synapses. He graduated in 2006 and then moved to Genentech where he began his studies of axon guidance with Marc Tessier-Lavigne. When his adviser moved last year to Rockefeller University in New York, Jaworski moved with him.
When he interviewed for the position at Brown – “Brown has a really great history and the undergraduate population here is supposed to be among the best you can find in the country,” he said – he met not only fellow neuroscientists but also members of the Department of Molecular Biology, Cell Biology, and Biochemistry. He said he felt very comfortable.
“It feels almost like a family, which is really not true for most places,” he said. “I remember how collegial it felt, how collaborative it felt, how welcome I felt.”
At Brown, Jaworski will continue to work on figuring out axon guidance, he said, but he’s also excited to branch out farther, so to speak, by looking at the migration of neurons, the formation of synapses, and how the connectivity of neurons that bridge the two halves of the spinal cord relates to their function.
It’s the perfect time to begin new research. In his new job at Brown he’s like a neuron that has made a transition from one context to another. And so he has new paths he can follow and new connections to make.