Neuroscientist Sonia Mayoral is known for her work studying the interactions of the cells that myelinate axons, but she said she started investigating those cells by chance.
Mayoral joined a lab at the Mayo Clinic in 2003, where she was introduced for the first time to glia, cells that provide supporting functions to the nervous system. She became especially interested in one type of glial cell: the oligodendrocyte, which produces the myelin sheath insulating neuronal axons.
Now, Mayoral has joined Brown University and the Carney Institute for Brain Science as the Robert J. and Nancy D. Carney Assistant Professor of Brain Science. She continues to study neuronal-glial cell interactions, but she is also interested in the role of myelination in neuroprotection, such as during neurodegeneration. Myelin greatly increases the speed at which axons conduct the electrical impulses they use to communicate to one another. However, Mayoral’s work is beginning to reveal new roles for myelin along axons, which involve the induction of local changes in the composition of the intercellular components of myelinated axonal regions.
“These local changes can affect the integrity and function of myelinated axons in a multitude of ways that I’m very excited to explore,” Mayoral said. “I’m interested in studying these first in the visual system, where I can genetically manipulate myelination along axons in the optic nerve.”
Mayoral conducted postdoctoral research at the University of California, San Francisco, where she developed a novel genetic mouse model that allows spatial and temporal control of myelin deposition along axons in optic nerves. Below, she explains how she will use this model to study the interactions between neurons and oligodendrocytes, and she discusses her plans for her lab at Brown and what led her to pursue a career in neuroscience.
What brain function problems are you most interested in solving, and how does your research help address those questions?
I’m interested in answering basic questions about how different types of brain cells interact with and support each other with a main focus on oligodendroglial interactions. I’m interested in uncovering the signals that oligodendrocyte precursor cells (OPCs) use to determine when they should divide or differentiate into a mature, myelin-making oligodendrocyte and where the signals come from. I’m also interested in better understanding how myelinating oligodendrocytes support and protect neurons and how neurons support oligodendrocytes. I believe the answers to these questions can have far flung impacts on how we approach the treatment of brain disease.
Your lab uses biochemistry, imaging and genomic analysis to study the interactions between neurons and oligodendrocytes. What are your plans for teasing apart the cellular and molecular mechanisms mediating these interactions?
To better understand the signals that guide oligodendrocyte development, I plan to use gene expression analysis methods to uncover the signals that are switched on or off at the time of oligodendrocyte differentiation during development, and then use in vitro co-culture systems to screen the signals for roles in promoting or inhibiting oligodendrocyte differentiation. I plan to then test the signals in vivo using viral overexpression and CRISPR, a gene editing technique.
To better understand how oligodendrocytes support neurons, I plan to use mutant mouse strains that have altered myelination, in particular a mouse strain that lacks oligodendroglia and myelin along the optic nerves, which are normally highly myelinated. I plan to examine differences in axon structure and function along unmyelinated axon segments and myelinated segments using super resolution microscopy methods, as well as methods that examine local protein production and transport functions along axons.
Are there aspects of Brown University and the Carney Institute that will be particularly helpful in advancing your research?
Yes! The community of researchers at Brown will be a huge asset to my work. There are researchers here with expertise on several aspects of my planned research — from imaging methods to gene expression analysis to examining axon structure and function — whom I’m very much looking forward to collaborating with and being mentored by.
The Carney Institute’s focus on neurodegenerative disease research will also be helpful to my studies since I believe the findings of my work will have big implications for the treatment of neurodegenerative disorders. Brown and Carney also have the resources and support mechanisms I need to lead a successful research program.
What led you to pursue a career in brain science?
My first undergraduate lab research experience. I didn’t know what lab research was until college. I heard that there was a program that supported underrepresented minorities doing research, and I wanted to learn more about it. It was the MARC program and to participate you had to find a lab to work in. I reached out to a faculty member conducting genetics research. He studied semaphorins, molecules that had guidance roles most notably in the nervous system. I began a project in his lab where I cloned an understudied fruit fly semaphorin gene with the goal of then studying its role in the fly nervous system. Ultimately, I never got to work with actual flies, but I thought a lot about how semaphorins and other molecules helped to build a brain, and I became fascinated about how such a complex structure develops. I’ve continued to be fascinated by this ever since.
Sonia Mayoral holds a B.S. in biological sciences from San Jose State University in California and a Ph.D. in neuroscience from Stanford University. She received an Institutional Research and Academic Career Development Award to conduct postdoctoral research at the University of California San Francisco.