Nervous System Development and Function

Whitehead Institute researchers are making important insights into the biology of the brain, from how it develops to what goes awry in neurodegenerative diseases and neurodevelopmental disorders.

Oligodendrocyte image.

Credit

Olivia Corradin/Whitehead Institute

Our Focus

The brain is a complex organ, and much of its biology remains to be discovered. Teasing out the specific mechanisms that help a healthy brain develop, or that may go awry in disease, can be a challenge—especially given that researchers have no real access to patients’ brain cells over the course of development or disease. Our researchers are developing new solutions for how to investigate the brain and discovering many important, informative aspects of brain biology.

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Making an inaccessible organ accessible

One challenge of brain research is the brain’s inaccessibility. Our researchers are advancing technologies and processes to build better models enabling a fuller picture of brain and central nervous system development. They are inventing ways to make stem-cell-derived brain cells behave more like cells in a live brain, and using brain organoids, three-dimensional assemblies of cells that form an approximation of brain tissue, in order to study cells in conditions that more closely match their environment in the body.

ZEISS Microscopy / CC BY 2.0.

Neurodevelopment and neurodegeneration

Scientists at Whitehead Institute are studying typical brain and nervous system development, as well as diseases and disorders of the brain, including neurodegenerative and mental health disorders. In order to understand these processes, they are looking at the roles played by individual genes, networks of genes and genetic regulators, and intra- and intercellular pathways. For instance, our researchers study diseases like Zika virus disease, which affects brain development and head size in a developing fetus, in order to learn more about the disease and also in order to gain insights into brain development.

Devon Svoboda

Misfolding, aggregation, and disease

In neurodegenerative diseases, such as Alzheimer’s, neurons can be negatively impacted by the aggregation of misfolded proteins and, potentially, misfolded RNAs, that build up in the cells and disrupt normal processes. Whitehead Institute researchers are investigating the causes and characteristics of these disease-linked aggregates.

Major Achievements

Discovery of harmful RNA aggregates

Whitehead Member Ankur Jain has discovered that certain RNAs can form aggregates, clumping together into membrane-less gels. This process, known as phase separation, has been widely studied in proteins but not in RNA. He has found that RNA gels occur in, and could contribute to, a set of neurological conditions such as amyotrophic lateral sclerosis and Huntington’s.

A new system implicated in multiple scelerosis

Fellow Olivia Corradin and her lab investigate disease-associated DNA sequence changes called genetic variants—slight differences in the same DNA sequence that vary from person to person—that are risk factors for MS. Their key discovery, published in 2020, was that immune cells are not the only cell types implicated in the development of MS; rather, genetic variants that affect cells in the central nervous system also appear to contribute to the disease.

Scientists