In the beginning, and at the end, it is all about the proteins, the building blocks of life.
Huda Zoghbi, renowned neurogeneticist, is particularly concerned with one protein: MeCP2, and the gene that encodes it. After eluding her for 16 years, MeCP2 presented itself as the gene which, when mutated, causes the neurodegenerative disorder: Rett Syndrome.
In 1999, over two and a half decades after she got on the case of Rett Syndrome, occurring primarily in females, Prof. Zoghbi, professor of paediatrics, Neurology, Molecular and Human Genetics and Neuroscience at the Baylor College of Medicine, and her team unearthed MeCP2.
She was speaking at the second leg of the Cell Press TNQ Distinguished Lectureship Series 2014 in Chennai on “A Journey from the clinic to the Laboratory to Understand Brain Disorders.”
The lecture was dedicated to the late Obaid Siddiqi, a celebrated biologist.
She said the lack of, or excess of, the protein (MeCP2) in a human being causes a spectrum of symptoms including impaired memory and learning, and social interaction, a peculiar wringing of the hands, loss of balance, abnormal activity, spasticity, all characteristic of Rett Syndrome, but also shared with other conditions, including autism, and MeCP2 Duplication Syndrome, more common among males. Clearly, the protein is big and causes a range of dysfunctions, and over 2500 genes are affected by MeCP2, Prof. Zoghbi explained.
Given that MeCP2 modulates the number of synapses, or points where neurons communicate with each other, it made sense to study the way these neurons work in mice models, she added.
Throwing up, in her presentation, an animation that roughly resembled the night sky with green star-like points flashing on and off, Prof. Zoghbi explained how neurons fired in a certain pattern, and in the case of the two MeCP2 conditions, how they fired in greater synchrony than in a normal person.
This showed that the networks may be affected similarly, whether there was a lack or excess of the protein, she added.
“At the end of the day, how a network behaves accounts for the way a person behaves.”
Calling them “circuit dynamics,” Prof. Zoghbi said studying them in MeCP2 disorders will provide insights into behavioural consequences.
The big hope, she said, is that this will lead to researchers coming up with viable therapies that would help people with MeCP2 mutations.
Prof. Zoghbi was introduced by N. Ram, chairman, Kasturi and Sons. Mariam Ram, chairman and managing director, TNQ India, and Emilie Marcus, Editor-in-Chief and CEO, Cell Press, also spoke.