Understanding the Scaffolding of Cells: The Cytoskeleton
Susan Parkhurst, Cellular and Molecular Biologist
Recipient, Mark Groudine Chair for Outstanding Achievements in Science and Service
It can be a harsh world out there for a cell. Major and minor injuries, such as a cut or contact with harsh chemicals, can cause a cell’s external membrane to tear, allowing its insides to leak out. This is terrible news for a cell. Even regular day-to-day activity — such as cardio exercise — can pose a threat, as the beating of our hearts slightly damages the membranes of our heart cells as they are stretched and pulled. The health of our organs depends on the health of the cells that make up those organs. It is crucial that cells quickly repair any injuries else they risk dying themselves — or worse, jeopardizing the whole body.
When looking at a cell under a microscope, it can often appear as nothing more than a formless blob, somewhat akin to a tiny water balloon. But in reality, our cells have a complex network of microscopic structures, called the cytoskeleton, that gives them shape and provides a scaffolding for many cellular processes. Cell signaling, migration, structure, and wound repair all depend on the cytoskeleton. Furthermore, cytoskeleton dysregulation is a common hallmark of cancer and can cause neurodegenerative, cardiovascular, muscle degenerative, and skin blistering diseases. The fact that the cytoskeleton underlies so many aspects of our health inspires Dr. Susan Parkhurst to better understand its organization and function — discoveries that could help further regenerative medicine and strategies to improve the body’s own repair mechanisms to heal damage.
Long before forming her lab at Fred Hutch, Parkhurst grew up in a military family and spent her grade-school years moving around the country. She remembered it being particularly challenging for her teachers to sync her curriculum between the many different schools she attended. The result was that she was often placed in independent studies, where she would work one-on-one with instructors. Instead of the typical high school science curriculum, her teachers asked her to read and report on research papers — a difficult proposition for a college student, let alone a high schooler. Despite the challenge, this sparked the idea of becoming a scientist, Parkhurst said.
“I liked how they were solving puzzles. I liked the challenge of having to figure things out,” she said.
No one in her family had yet attended college, let alone pursued a career in research. Undeterred, Parkhurst looked at the top of the scientific papers she had been assigned and saw John Hopkins University.
“Okay,” she thought, “I want to go there.”
Parkhurst applied, was admitted, and became the first person in her family to go to college.
Almost as soon as she stepped foot on campus, she sought opportunities to join a lab and start doing research. She found a cancer research lab that gave her the freedom to develop her own project, a rarity for many undergraduates. For Parkhurst, the best part of college was that she could spend as much time as she wanted in the lab.
“As soon as I started, I thought, this is me, this is what I like doing,” she said.
Committed to a career as a scientist, she applied to graduate school at John Hopkins, where she jumped right back into research. It was in her graduate lab that she fell in love with the tiny animals she still uses to explore biology: fruit flies.
“Fruit flies are great because I can do experiments all day, every day… even all night!"
The fruit fly is one of the preeminent model systems for investigating fundamental cellular processes because its underlying biology is often shared with humans. A new generation of fruit flies can be raised in about ten days. This makes them a hassle in your kitchen but a fantastic tool for scientists interested in the essential underpinnings of cellular biology.
Parkhurst loved working with these tiny insects because “things could move very fast, and I was impatient,” she said. “Fruit flies are great because I can do experiments all day, every day… even all night!"
Fruit flies — and the speedy research they make possible — remain a cornerstone of Parkhurst’s science. She’s still often at the bench alongside her lab members studying how cells maintain and control their structure and how disruptions in these processes can prove detrimental to our health.
The cytoskeleton’s network of protein filaments links cellular components together and gives cells get their rigidity and shape. Importantly, the cytoskeleton helps maintain the structure of two of the most critical parts of our cells: the external membrane, which separates the inside of a cell from the outside, and the nuclear membrane, which protects and houses the cell’s genetic material. Damage to these membranes, whether as the result of physical injury or normal cellular processes, can quickly prove lethal to a cell or lead to DNA damage, possibly causing cancer. It is vital to understand the dynamics and processes of how cells maintain and repair their structure both at a cellular and organismal level to develop better treatments and therapies for numerous diseases, including chronic wound disease and cancer.
Researchers have been studying wound healing for decades and have a good grasp of the physical changes that occur during healing, but there is still limited understanding of which molecules are involved and how their interactions unfold over time, Parkhurst said.
“We don’t know what the start signal is, how your body knows it’s wounded, how it knows the correct way to heal, and how it knows when it’s done healing and can stop. We may know many parts to the process, but no one understands the complete biochemical pathway,” she said.
To answer these questions, her lab explores the genes involved in healing.
“Genetics lets you take a systematic approach and identify all of the genes required for wound healing. Once you know the genes, you can figure out their order of action,” Parkhurst said.
This approach has allowed the lab to learn that how you are wounded matters. For example, a cell wounded with a laser will give a different biochemical healing response than a cell wounded by a mechanical puncture.
Understanding these differences will help scientists figure out how to direct cells through the correct healing process. This is why Parkhurst believes that understanding the fundamental biological mechanisms behind these processes are so important.
“If you want to fix something, you need to know what the underlying principles are, what went wrong, and what options you have to make it right,” she said.
— By Matthew Ross, April 14, 2022
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