With fluorescent stem cells and an online portal, the Allen Institute for Cell Science is delving into life’s basic building blocks to boost the quest for cures.
Everyone knows what a cell looks like, right?
Standard textbook illustrations show a membrane, a nucleus and the tiny power plants called mitochondria. But diagrams like these don’t come close to capturing the complexity in even the simplest of cells.
Now, Seattle’s Allen Institute for Cell Science is offering a new way to peer into the inner workings of cells.
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The Allen Cell Explorer, which is being unveiled Wednesday, is an online portal to stunning images of living cells, along with a suite of digital tools to help researchers study normal cells — and what goes awry when disease strikes.
The portal provides access to the world’s largest public collection of three-dimensional images of human stem cells. Users can rotate the images on their computer screens and zoom in on structures tagged with glowing, fluorescent dyes. Time-lapse movies on the site show how cells interact and change over time.
“It allows anybody to get a view of these cells, even if they’re not scientists,” said Susanne Rafelski, a manager and cell biologist at the institute. “It’s fascinating.”
The project draws on more than two years of work at the cell institute, founded in late 2014 with a $100 million grant from Microsoft co-founder and philanthropist Paul Allen.
The institute takes an industrial-scale approach to the study of cells, starting with an array of high-tech instruments that no single researcher could ever replicate. Teams of biologists, computer scientists and technicians collaborate on ways to process and share vast amounts of data. The institute also develops techniques and tools that are made freely available for other researchers to use.
One of the most potentially powerful tools is a computer model that attempts to mimic a living cell. The first-generation version, available through the Allen Cell Explorer, is able to predict how cellular components, like mitochondria and a kind of scaffolding called microtubules, are organized in normal stem cells, said Graham Johnson, a lead researcher on the project.
“Right now, we’re taking baby steps to understand how cells are organized, and their architecture,” Johnson said.
Next, the team hopes to improve the model so it will be able to predict how stem cells change as they develop into different body tissues, and how disease upsets that progression.
The institute’s human stem cells are derived from adult tissue that has been coaxed back into a kind of embryonic state. That gives them the potential to develop into heart cells, skin cells or virtually any other type of tissue.
Institute scientists have developed 10 stem-cell lines, genetically tagged with fluorescent dyes that cause different structures to glow. The cells are provided at a nominal cost to research labs around the world.
University of Washington biologist Benjamin Freedman uses the cells in his search for ways to regenerate failing kidneys.
In his lab, Freedman nudges stem cells to develop into small assemblages of kidney tissue he calls organoids. The fluorescently marked cells allow the team to film the process.
“We can watch in real time, not just the cells moving around, but the organelles, the subcompartments inside the cells,” Freedman said. “It gives us a sense of how the structures of the cells are changing and moving during this complex process of kidney formation.”
He hopes to someday be able to extract cells from a patient with disease and reprogram them into healthy kidney cells that can be transplanted back into the body. But first, he and his colleagues need to understand much more about how normal kidneys develop and how disease throws a wrench in the organ’s function.
Even for diseases with a clear genetic link, scientists still have only a fuzzy idea of how the pathology arises and progresses, Freedman said.
“We need to understand what’s happening in these diseases at the cellular level and how that affects the tissue if we’re ever going to be able to treat the root cause of the disease and not just the symptoms.”
In addition to improving their computer model, Allen Institute researchers are continuing to refine their tools to help researchers like Freedman, Graham said. They hope to produce even sharper, three-dimensional cell images and more stem-cell lines.
They also want to add educational tools to the website to make what’s now a very technical interface more accessible to students and the public.