Academic, Industry Labs to Build Brain Cell Models

Neurons (Laura Struzyna, University of Pennsylvania, NIH.gov)

24 Nov. 2023. Researchers from university labs in the U.K. are developing models of brain cell interactions using a company’s synthetic human cells derived from stem cells. The initiative brings together neuroscientists and cell biologists from the biotechnology company bit.bio — the name is spelled in all lower-case — in Cambridge, U.K. and the Institute of Psychiatry, Psychology and Neuroscience or IoPPN at Kings College London.

bit.bio is a six year-old business developing synthetic human cells for research and drug discovery, spun-off from labs at University of Cambridge. The company says its technology called opti-ox, short for optimized inducible overexpression, enables the design of human cells with specific properties and characteristics. The opti-ox process, says bit.bio, is similar to software programming, where the code in this case, is the cell’s genetics. The company says it alters the genome of induced pluripotent stem cells, so-called adult stem cells, with transcription factor proteins that regulate instructions delivered to cells with messenger RNA.

According to bit.bio, this process can be applied to a wide range of human cells, with its main product line called ioCells. One of the company’s applications is a line of synthetic cells for research derived from healthy human donors called ioWild Type Cells. Among the synthetic cells bit.bio offers in this line are neurons or signaling cells in the brain with genes expressing glutamate proteins regulating memory, cognition, and mood, and neurons with genes expressing gamma aminobutyric acid or GABA proteins that limit brain signals, associated with anxiety, stress, and fear. A third ioWild Type Cell are microglia cells that perform repair and maintenance functions in the brain.

Multi-cell models to reveal complex brain processes

Two neuroscientists at IoPPN plan to generate models of interactions among brain cells with ioCells. Deepak Srivastava is a molecular biologist and Anthony Vernon is a pharmacologist, both studying functions of neurons and microglia, including those derived from human pluripotent stem cells. The team expects to build models of brain cell interactions for revealing complex processes in the brain that cannot be demonstrated with single-cell models. For example, says bit.bio, impairment of one cell type may affect the functioning of other cells in the brain.

The company says Srivastava and Vernon already worked with its synthetic cells and are familiar with their properties. “It’s the unique properties of bit.bio’s ioCells,” notes Srivastava in a bit.bio statement, “that will enable us to create a consistent and scalable multi-cell model.” Srivastava adds, “These properties significantly reduce potential concerns that variability in experimental data could be due to variation in the cells in our models.”

Vernon cites schizophrenia as an example where complex brain cell models can better understand how treatments for the disease work. “Whilst antipsychotic medications can be effective,” says Vernon, “they do not address all symptoms of schizophrenia and a significant proportion of individuals show no therapeutic response to these agents. Moreover, they are associated with significant side effects.”

bit.bio says it expects the collaboration with King’s College to run for three years, with the resulting models released to the larger academic community.

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