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brain

Philip Spyrou in the Spotlight

December 9, 2024 by Noah Zuijderwijk

“The lab and the art studio are fundamentally the same space; you have a material, a question you want to answer, and you experiment” – Philip Spyrou

Give a teen unfettered access to the internet and they might transform into a brain-rotten screenager. Luckily, in Philip Spyrou’s case, hours spent looking at Reddit feeds and YouTube videos did not translate into cognitive decline. In fact, quite the opposite was true; he used his internet privileges to teach himself how to cultivate life. As a high school sophomore, Philip experimented with hydroponics and tried to grow mushrooms using soil he made with whole grains and a pressure cooker. His resourceful and creative fascination with life led him to a chemistry and visual arts double major at Bowdoin College. He now studies the role of proteins in neuron function as a senior researcher in Professor Henderson’s chemistry lab.

When Philip showed me around the Henderson lab, he explained that proteins play a near-infinite number of crucial roles in biological processes. One such process is the formation of synapses in the brain. In simple terms, a synapsis is the coming together of two neurons to exchange information – a crucial mechanism for routine brain function. However, neurons need the ability to “crawl” around brain tissue before they can find other neurons and form synapses. SRGAP proteins enable neurons to develop finger-like protrusions from the cell membrane with which they can “crawl”. Philip studies how the membrane attracts these proteins.

Though one might think studying neurons requires a lab furnished with preserved brains in glass jars, Philip’s research (disappointingly) does not involve Frankensteinian techniques. In fact, Philip works with model cells called Giant Unilamellar Vesicles (GUVs), which are artificial membrane systems used to study cell functions. By modifying the GUV’s membrane, he observes how different membrane compositions attract SRGAP proteins. These observations can then be mapped onto neurons to understand how they develop the ability to “crawl” through brain tissue.
 

To study this neuron crawling mechanism, Philip has to think beyond the two dimensions of a textbook. After all, a protein’s three-dimensional structure is key to its function. In this regard, his time in the art studio has proven valuable to his work in the lab. Philip believes the lab and the studio aren’t all that different, and that working with clay and ceramics has trained him on how to gather materials, ask questions, and design experiments with a three-dimensional mindset.

 
 

“I like thinking visually, structurally, and three-dimensionally about the biological processes I study”

 

 
 
 

The three-dimensionality of Philip’s research unfolds at the molecular scale. It requires him to spend most of his time thinking about intangible processes. But, he says, it helps him to think of the applications of his research. For example, loss of proteins that enable neuron cells to crawl around the brain might be implicated in cognitive disabilities and memory loss. This is something he hopes to continue researching by earning a PhD with the goal of eventually becoming a full-time researcher.

As Philip continues on this path toward becoming a scientist, he finds it important to keep reminding himself of where his passion for science comes from. His love for understanding life originated in his backyard when he figured out how to grow plants and mushrooms. Though he does not foresee himself going back to researching those forms of life any time soon, he does want to keep tapping in to his fifteen-year-old self’s creative fascination for life.

Filed Under: Honors Projects Tagged With: biochemistry, Biology, brain, chemistry, honors, neuron, neuroscience, student

Distributions, not Differentiation: New Studies Find Cell Proportions at the Heart of Neurological Specialization

December 3, 2023 by Vincent Chen '27

The human brain is organized into cortices, lobes, hemispheres, and more, with every designation serving as a location where a particular function necessary for survival is hosted. In understanding the cell types of the brain, scientists can further shape the understanding of the nature of human life. Current work strives toward comprehending the functions and capacities of the brain and developing stronger foundations for modeling brain physiology to support future research and medical applications. All of the advancements discussed originated from Alyssa Weninger and Paola Arlotta’s Science review article, A family portrait of human brain cells, which compiles recent findings in brain mapping research as aligned with the National Institute of Health’s BRAIN Initiative. In the article, Weninger and Arlotta summarize and discuss the work of multiple groups of neuroscientists that have developed new findings about the brain’s composition and variability across regions, individuals, and species (specifically five primates of interest and mice).

As suggested by the article, recent research from multiple teams of neuroscientists utilized a variety of study mechanisms to compare the composition of the brain. One of the most important tools used in the studies included single-cell profiling. This profiling technique analyzes cellular behavior through multiple methods that include their transcriptome (range of genetic information produced to control cell behavior), proteome (range of proteins produced by the cell), and epigenome (range of modifications and markings that control the genetic information expressed by a cell) to organize them into groups based on their functional similarities. Models that encompass these methods and human organoids (structures of organs derived from STEM cells that mimic organ tissue) are developed to model the brain and its cells. They are also used in mapping and developing comparative analyses to determine significant findings and understanding of the brain organization.

Comparisons of cell composition in regions across the brain resulted in findings from researchers under Siletti from the University of North Carolina at Chapel Hill and Jorstad from Harvard University. The two groups found that rather than mainly having different types of cells in different parts of the brain, some different parts of the brain shared the same cells but had different proportions of these cells. There were some exceptions, such as inhibitory neurons in the primary visual cortex, although the explanation of this finding is unclear. Such results change the understanding of evolutionary diversity in that diversification does not depend heavily on having many different cell types, but rather on having varying proportions of cells with small differences.

Jorstad’s group also developed a significant result in identifying differences in brain composition between human individuals. One cell type from 75 individuals was profiled and resulted in different classes of cells bearing contrasting levels of variability among individuals. Most of the explanatory factors were beyond demographic differences, such as gender, ancestry, or age. The reason for such differences is still unclear. Scientists are further encouraged to study bigger cohorts of people to further examine the origin of differences in variability across humans.

The finding of varying cell proportions held as Jorstad’s group conducted interspecies comparisons, comparing human compositions with other primates (specifically chimpanzees, gorillas, rhesus macaques, and marmosets). The exceptional cognitive ability found in humans was largely supported by differences in proportions of brain cell types rather than the variability of cell types. Additionally, faster evolutionary divergence may explain the differences in gene expression found between supportive tissue, known as glial cells, in the brain. This allowed for further species-specific development across primates. Only a limited number of gene patterns specific to humans were found, most of them concentrated in parts of the brain with human evolutionary change. As such, scientists have come to understand that attributes of the human brain are derived from very few cellular or molecular changes, leaving differences in cell proportions as the most prominent explanatory factory for human brain development. Furthermore, understanding the brains of related primates and their relation to human brains will help scientists develop new models for brain pathways and understand the kinds of questions that they will be able to answer with such knowledge in the future.

Neuroscientists today continue to work hard toward developing human brain models. Current studies are focusing on developing accurate organoids – three-dimensional tissue models of stem cells developed to mimic organs in structure and function. Velmeshev’s group of researchers worked towards profiling different cortical (outer layers of the upper brain) areas and related areas in fetuses to track developments across human births. Kim’s group of researchers investigated single-cell transcriptomes of the thalamus (the processor of sensory data) during its development but was missing an investigation of the thalamus cellular compositions. The work of these scientists contributes to the idea of molecular mechanisms as the driver of cellular diversity in the brain, but also calls for more innovation in external biological investigations to better model the brain and further study its composition. In doing so, neuroscientists will come even closer to understanding one of the most complex systems in the human body and develop more answers for current-day neurological problems.

Bibliography

Weninger, Alyssa, and Paola Arlotta. “A Family Portrait of Human Brain Cells.” Science, vol. 382, no. 6667, Oct. 2023, pp. 168–69, https://doi.org/10.1126/science.adk4857.

Filed Under: Psychology and Neuroscience, Science Tagged With: brain, brain cell proportions, BRAIN Initiative, mapping, models, profiling

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