Solving DNA Puzzles, One Worm at a Time

By Julia Halprin Jackson

​L-R: Idan Siman-Tov, ’19 Biological Sciences, Veronica Bi, ’20 Biological Sciences, Jordan Mitchell, ’19 Biological Sciences, Nebat Ali, ’19 Biological Sciences, Muhammad Taha Muqtadir, ’19 Biological Sciences, Anjana Baradwaj, full-time research associate and Miri VanHoven. Photo courtesy of Miri VanHoven.

“Education is the great equalizer in society. If you come to a place like SJSU, that has this huge proportion of first-generation college students, you really have this opportunity to make the world a better place.”
–Miri VanHoven

W​hen she was a child, Miri VanHoven spent many Saturdays at the San Francisco Academy of Sciences with her father, a NASA physicist. She loved watching the dolphins who used to inhabit a tank in the Steinhart Aquarium, and was fascinated by the way they behaved and interacted. In high school, she discovered cell and molecular biology, which captured her imagination because it offered insight into how scientists could potentially cure diseases by examining organisms at the cellular level.

“If you want to cure a disease, you have to understand the underlying biology,” says VanHoven, associate professor of biological sciences at San Jose State. “If you can figure out what goes wrong at the molecular level in that disease, you can fix it. Basic biology research leads to cures the vast majority of the time.”

Armed with that knowledge, VanHoven discovered a passion for neuroscience in graduate school. There were still so many unanswered questions about the nervous system left to explore. How do neurons transmit messages throughout the body? How are circuits formed? What are the genetic differences between healthy individuals and those living with neurological disorders? And how can studying these genes lead to therapies, drugs and treatment?

“Many of the genes we have studies that have turned out to be involved in different steps of neural circuit formation are also linked to autism and schizophrenia, which indicates these neurological disorders likely have underlying circuit formation defects,” she says. “One of the reasons we are so far from finding cures is we don’t understand the molecules that are involved, which means we can’t understand what’s going wrong in order to fix it.”

Decoding Genetics

L-R: Anirudh Bokka, ’20 Molecular Biology, Miri VanHoven, Aruna Varshney, ’12 MS Biological Sciences, lab manager; Nebat Ali, ’19 Microbiology. Photo by Josie Lepe.

Not long after VanHoven arrived at San Jose State in 2008, she established a neurogenetics lab to explore these questions with a team of undergraduate and graduate student researchers. They use a model organism, a tiny, transparent roundworm called C. elegans. Because the worm is optically clear, scientists can observe it without dissecting or destroying its nervous system, which is remarkably similar to our own. VanHoven explores how the nervous system is formed and how potential genetic misfires may cause diseases such as autism and schizophrenia. She has secured funding from the National Science Foundation and the National Institutes of Health to support this research.

In order for her team to understand how these diseases originate, they must first identify the way these systems normally work. They introduce mutations to the worms to remove the function of specific genes and observe how the organism responds, thereby learning the specialized functions of each gene—a scientific process of elimination.

In addition to investigating the formation of the nervous system, VanHoven also explores learning and memory. The worm has a capacity to learn and develop memories—a skill that VanHoven and her team can better understand by visualizing connections between cells in the nervous system, called neurons, using fluorescent microscopy. Starting in 2013, she partnered with Noelle L’Etoile, associate professor of cell and tissue biology at UCSF, to pursue the NIH grant funding necessary to explore these questions with her lab. By observing these connections before, during and after memory formation, students can observe the physical changes that underlie memory development. Similar changes are thought to underlie human memory formation, but they are much harder to study directly.

Long term, VanHoven believes understanding how synapses form and how they are modified during learning and memory will help scientists pinpoint what causes autism, schizophrenia and forms of dementia, thus making it possible to intervene, treat and possibly cure them. She enjoys sharing this research process with her students.

“The National Science Foundation says it is important in undergraduate biology education to offer meaningful experiences that help students understand what research is really like,” VanHoven says. “Otherwise they don’t understand where all the facts are coming from. That’s a big loss, because then they can’t discern what is good research or make decisions that are based on research. It is especially important that they understand how science is done so when they read these studies and apply them, they really understand the meaning of that data.”

“Science is the only way to determine how the natural world works. The more we understand how things work, the more we can change them to our benefit.”
-Benjamin Barsi-Rhyne, ’13 Biological Sciences

Her alumni have gone on to apply the skills learned in her lab to graduate research and careers in biotech. Ben Barsi-Rhyne, ’13 Biological Sciences, learned about VanHoven’s lab as a sophomore. Intrigued by how brains allow us to think, he was amazed to learn that her lab offered hands-on research experience for undergraduates, a rarity in many academic environments. While many research universities establish labs that are spearheaded by graduate students and post-docs, at San Jose State these same responsibilities are managed by undergraduates who are overseen by their professors. This means that many of the students graduating from VanHoven’s lab are departing with years of graduate-level research experience, which sometimes includes contributing to major publications.

During his time in the lab, Barsi-Rhyne learned the basics of fluorescent microscopy, honed his critical thinking skills and stayed an additional year to publish his first scientific paper. Now a PhD candidate in molecular biology and biochemistry at UCSF, he says that he arrived in San Francisco with more research experience than most of his cohort, many of whom attended private universities, Ivy League colleges and UCs.

“The implications of Professor VanHoven’s work are quite large,” Barsi-Rhyne says. “Her lab can identify proteins that have a role in forming or maintaining synapses in the relatively simple nervous system of a worm. Other scientists can then determine if these or similar proteins exist in people and if they are connected to neurological disorders.”

At UCSF, Barsi-Rhyne has turned his attention to G-protein coupled receptors, proteins on the surface of cells that detect changes in the extracellular environment. He is specifically focused on a molecule called arrestin, whose job it is to alter signals sent by these receptors.

“In order to design a treatment for something, you need to understand the underlying processes that you are trying to alter or fix,” Barsi-Rhyne says, a concept he first learned in VanHoven’s lab. “That’s the ultimate goal of the work I’m doing: to help us understand how these signals are generated and how they are turned off. Hopefully that understanding will lead us to deeper insights or the ability to design novel therapies.”

From Research to Application

Scientists performing basic research construct the biological foundation others need to develop drugs, therapies and treatments. Much in the way a building first needs a strong frame, biologists need a fundamental understanding of how cells work and what functions they serve before they can determine how to solve problems. Clinicians, doctors and medical students often look to the latest research to update their approach to treatment, says Miguel Moreno, clinical associate professor of neurology and neurological sciences at Stanford. A practicing neurologist, Moreno, ’94 Biological Science, works with children living with a variety of neurological disorders, including epilepsy, developmental delays, migraines and cerebral palsy. Since becoming a doctor, he’s seen how research contributes to improved treatment, especially for conditions like muscular atrophy.

“The education at San Jose State really helped prepare me for my medical school work and beyond.”
–Miguel Moreno, ’94 Biological Sciences

“When I first started, we didn’t have many treatments for muscular atrophy,” says Moreno. “With this condition, children are born unable to move, and their anterior cells in their spinal cord deteriorate, which means they lose muscle function, respiratory function and succumb to the illness rapidly. Within the last several years, though, with all the dedicated research, there’s a new treatment. As long as children get diagnosed quickly, which we can do thanks to advancements in genetic technology, we can provide them with treatment and they can do very well.”

When he supervises medical students and residents in his hospital rounds, Moreno says he keeps them updated on the latest research and practice guidelines. The stakes are higher when interacting with patients coping in real time. Moreno’s patients come to Stanford from as far south as Los Angeles, as far north as Redding and as far east as Nevada. The promise of research from places like VanHoven’s lab offers hope and promise to the doctor, who says his own Spartan experience set him up well for medical school.

“In the past, we were only able to offer some support, comfort and guidance to patients with some of these conditions,” Moreno says. “Now we can offer more interventions, more treatments, medications and even diets that we use to help people. It’s exciting now that there is a lot more we can do and a lot more that might be coming in the next decade.”

Next Steps

What is next for the VanHoven lab? In the past year, the professor has been awarded two new NIH grants–one to support the ongoing work on disease-linked genes functioning in synapse formation, and the other in collaboration with L’Etoile at UCSF to understand the underlying basis of memory consolidation. There are always more questions to ask, more challenges to overcome. VanHoven says scientific research and quality STEM education are critical not just to gain an understanding of how our bodies work, but ultimately to treat and cure diseases.

“Do you want autism to be cured? Do you want schizophrenia to be cured? Do you want Alzheimer’s to be cured? The list goes on and on,” VanHoven says. “If you do, we need science education and we need basic science research. That’s the only way you get to these things. All modern cures have emerged from STEM research, which is one of many reasons we need it.”

 

Julia Halprin Jackson

Julia Halprin Jackson is an advancement writer on San Jose State University's Strategic Communications and Marketing team.

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