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Scientists in this laboratory are exploring the molecular details of human — and other primate — brain cells
3 min read
For Brain Awareness Week 2022, we dropped in on five Allen Institute teams working to understand the brain. Get a glimpse into their workdays.
When we pop into the human cell types lab, Rebecca Hodge, Ph.D., is bent over a large metal trough with a tray inside — it’s a cold table, she says, for keeping frozen tissue cold as you look at it or dissect. A bucket of dry ice with open baggies is perched on the edge next to her.
Hodge is fiddling with a pinkish, frozen slab of brain on the table. It was taken from a macaque brain, and she’s looking for a certain region — the middle temporal gyrus, a section of your brain just behind your ear — for analysis.
She finds what she’s looking for and hands the tissue off to Anna Marie Yanny, another researcher in the lab. Yanny will use a technique called multiplex FISH that looks at whether and how much genes are switched on (a measure known as gene expression) in brain cells in the context of the tissue itself. Other gene expression analyses break up tissue into individual cells or a slurry of cells, but FISH allows the researchers to see different genes light up without breaking up the brain tissue, meaning they can pinpoint where different types of neurons and other brain cells reside in the brain.
Their goal is to understand the cellular makeup of this region of the brain and how it differs in closely related species. In other experiments, the researchers will look at the same region from human, gorilla, marmoset and chimpanzee brains. By looking at gene expression across the entire genome in individual brain cells from these different kinds of primates, the scientists can get a better understanding of how the different types of cells that make up our brains are similar or different to those of our closest relatives.
With multiplex FISH, Yanny and others on the Human Cell Types team are looking at a few cell types they’re particularly interested in to see where they reside in the brain.
Next to Yanny at the lab bench, neuroscientist JT Mahoney is surrounded by tiny tubes of clear liquid. Each tube contains DNA from a different human donor, he said — most of them are from brain donors who died with Alzheimer’s disease.
The tubes are part of a relatively new project at the Allen Institute, a center launched in 2020 to map the different types of brain cells most vulnerable to Alzheimer’s. Like the studies comparing brain cell types in healthy humans and other primates, the scientists studying Alzheimer’s disease want to understand whether the cellular makeup of the brain changes during the course of the disease.
They’re using similar techniques to catalog the brain cell types by comparing their gene expression, Mahoney said, and right now, the researchers are testing a few different techniques before they pick one that they will scale up. The tubes of DNA serve as reference points, so they can match data from the different methods back to the same donor.
Across the room from Mahoney and Yanny, the lab is bustling — several members of a group that works on gene therapy-related techniques for the brain have gathered for an early spring cleaning. These researchers work on special types of modified viruses that deliver fluorescent labels or other genetic cargo to a single cell type in the mouse, human or monkey brain. Eventually, these tools could be used to deliver gene therapies for genetic brain diseases and disorders.
Photos by Erik Dinnel, Senior Producer at the Allen Institute, and text by Rachel Tompa, Senior Editor at the Allen Institute. Get in touch at [email protected].