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Guo-li Ming on how neurons make connections in the brain:
When did you determine that you wanted to be a researcher?
MING: I decided to be a researcher later than most people. I first went to medical school in China and focused on child and maternal health and development. When I came to Columbia University to meet up with Hongjun Song, my husband and collaborator, I planned on taking the board exams to become a doctor, but I didn’t get around to it. I used to visit Hongjun at work where he was a graduate student and I found the research to be fascinating. Eventually, research appeared more interesting to me than going into clinical practice. I joined as a graduate student in Mu-ming Poo’s lab with Hongjun and continued to study neural development, but on a more basic level than I did in medical school.
What do you study?
MING: I am interested in how the neurons in the brain form connections to other neurons by reaching out feelers –axons and dendrites—to communicate and send electrical impulses to one another. We study these neural developmental processes during both embryonic development and in the adult brain.
Why is this process important?
MING: Proper brain function —critical for everyday life--depends on proper connections between neurons themselves and between neurons and other cells in the body. So understanding how these connections are formed not only is essential for understanding the biology of neurodevelopment, it can also shed light on nervous system repair, a process that can be disrupted by injury or diseases.
For example, schizophrenia is one devastating psychiatric disease suggested to have a neural developmental origin. About a decade ago, researchers discovered that a Scottish family’s high incidence of bipolar disorder and schizophrenia could be attributed—through genetic studies of this family—to mutations in the protein DISC1, which stands for ‘disrupted in schizophrenia 1.’
Recently, we’ve found that this same DISC1 protein regulates how neurons migrate and how the axons and dendrites form connections during brain development in mice. Now we are also trying to use neural cells derived from induced pluripotent stem cells (iPSCs) from patients with psychiatric diseases to examine neuronal development and try to understand how mutations in the DISC1 gene may contribute to psychiatric disease.
Which other developmental disorders does your research impact?
MING: While we mostly focus on psychiatric diseases such as schizophrenia and autism, we also have compared iPS cells from patients with Trisomy 13 and healthy individuals and found that Trisomy 13 iPS cells exhibit developmental defects. Patients with trisomy 13 have three rather than the normal two copies of chromosome 13 and the condition is the only one of three types of Trisomy where babies can survive past birth. Trisomy 13 patients have profound mental retardation and defects in their brain and spinal cord. Using the trisomy 13 iPS cells, we are investigating the molecular cause of these developmental problems.
And your research is a family affair, you collaborate scientifically with your husband, Hongjun Song?
MING: Hongjun and I have been collaborating for over 15 years. Both of us share a strong interest in understanding how adult neurogenesis occurs and how it is regulated. But we have different focuses: his research is more on how the cells are born and my research centers more on neural development. For example, much less is known about how the adult born neurons make connections, whether they use the same basic mechanism during embryonic neural development or an entirely new method, and we hope to clarify this.
--Interviewed by Vanessa McMains
Guo-li Ming on studying brain development: