Home > Archives > June 2014 > Features > All in a Day’s Work: Melissa Rolls Excels as Researcher, Mentor, and Leader

All in a Day’s Work: Melissa Rolls Excels as Researcher, Mentor, and Leader

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2 June 2014

Scientists have different motivating factors when it comes to deciding what exactly they are going to study. For some, the thrill of discovering something new pushes them to pursue research in a particular field; for others, passion or experience in an area makes the topic an easy choice. For Melissa Rolls, one direction of her research at Penn State was guided by a suggestion from one of her lab technicians.

Rolls, an associate professor of biochemistry and molecular biology, came to Penn State in 2007 with the intent to continue her research in neuronal polarity. After getting this work off the ground and publishing her first paper, Michelle Stone, a research technician and part-time graduate student in Rolls’ lab, approached Rolls with a suggestion. Stone’s father had suffered a stroke that left him unable to work and function normally. Stone thought that the system the Rolls lab was using could be adapted to study how neurons, or nerve cells, respond to damage or injury; she wanted Rolls and her team to study neuronal injury to better understand it and potentially make a discovery that could aid future stroke victims.

Read about Michelle Stone in Person-to-Person.

Rolls considered the idea and together she and Stone came up with a strategy to add the study of neuronal stress and injury to the lab portfolio. She organized her lab into two parts in order to gain a full perspective on neurons and nervous system repair: half of the lab focuses on the foundation, which includes studying how neurons develop and function normally; the other half of the lab got to work investigating how neurons behave when injured.


Experimenting with Fruit Flies

Rolls chose to use Drosophilia, or fruit flies, as her model organism rather than mammalian cells. "On the molecular level, many of the processes associated with nerve-cell growth and regrowth are the same in humans as in fruit flies," Rolls said. "Discoveries can be made much more quickly and economically in flies. They also don’t bleed!"

Using fruit flies, the team discovered that the neuroprotective pathway initiated in response to injured or stressed neural axons serves to stabilize and protect the nerve cell against further degeneration. Neurons have a single axon that transmits signals to other neurons or to output cells. Because the axons often extended long distances within a cell, they are prone for damage. So, if an axon is damaged, its parent neuron can no longer function; and since many animals develop only one set of neurons, those neurons will mount major responses to axon injury.

Working in vivo, Rolls and her team severed fruit fly axons and discovered that neurons responded to the injury by increasing production of microtubules in order to stabilize the neural dendrites. The pathway represents an endogenous neuroprotective response to axon stress — and could potentially be developed into a diagnostic tool for the detection of early stages of neurodegenerative disease, or even utilized in novel therapies for such illnesses.

Axons ideally survive throughout an animal's lifetime. To be able to survive, nerve cells need to be resilient and, in the event of injury or simple wear and tear, repair damage by growing new axons. These microtubules might need to be rebuilt as an important step in this type of repair.

"In many ways this idea makes sense: in order to grow a new part of a nerve, raw materials will be needed, and the microtubule highways will need to be organized to take the new materials to the site of growth," Rolls said. The Rolls team therefore started to investigate the role of microtubule-remodeling proteins in axon regrowth after injury. In particular, the team members focused on a set of proteins that sever microtubules into small pieces. Out of this set, a protein named spastin emerged as a key player in axon regeneration.

Rolls and her team found that a mutation in a single gene could entirely shut down the process by which axons regrow themselves after being cut or damaged. "The fact that the spastin protein plays a critical role in regeneration is particularly intriguing because, in humans, it is encoded by a disease gene called SPG4," Rolls explained. "When one copy of this gene is disrupted, affected individuals develop hereditary spastic paraplegia (HSP), which is characterized by progressive lower-limb weakness and spasticity as the long-motor axons in the spinal cord degenerate. Thus, identifying a new neuronal function for spastin may help us to understand this disease."

The scientists also found that an impaired spastin gene affected only how the axons regrew after being severed. In addition, the researchers found that, while the gene affected the flies' axons, their dendrites continued to function and repair themselves normally.

"Now that we know that spastin plays an important role in axon regeneration and also that this gene is dominant, we have opened up a possible path toward the study of human diseases involving nerve-cell impairment," Rolls said.



SpastinIn fruit flies with two normal copies of the spastin gene, Rolls and her team found that severed axons were able to regenerate. However, in fruit flies with two or even only one abnormal spastin gene, the severed axons were not able to regenerate.
Credit: Rolls lab

 


The Rolls lab’s latest discovery involves a brand-new pathway for repairing nerve cells that could have implications for faster and improved healing.  These findings demonstrate that dendrites have the capacity to regrow after an injury. Despite it being a seemingly basic question, other scientists had not asked whether or not dendrites could regenerate.

Again using the fruit fly, the researchers took a radical approach by cutting off all of the dendrites in neuron cells. "We wanted to really push the cells to the furthest limit," she said. "By cutting off all the dendrites, the cells would no longer be able to receive information, and we expected they might die. We were amazed to find that the cells don't die. Instead, they regrow the dendrites completely and much more quickly than they regrow axons. Within a few hours they'll start regrowing dendrites, and after a couple of days they have almost their entire arbor.”

Based on this experiment, it was also apparent that dendrite regeneration happens independently of axon regeneration. When Rolls and her colleagues blocked the key signaling molecules that are required for axon regeneration in all animals, they found that dendrites were unaffected and continued to regrow. "This means that, not only do these neurons have an incredible ability to generate, they have two different regeneration pathways: one for axons and one for dendrites," she said.

As with her other research, this project yields an important real-world application. In the case of a stroke, when a region of the brain suffers blood loss, dendrites on brain cells are damaged and can be repaired only if blood loss is minor. Otherwise, it is thought those brain cells die. However, if those cells are able to regenerate dendrites, and if scientists learn how dendrite regrowth happens, researchers may be able to promote this process.



DendritesThis image shows a single nueron in a whole animal five hours after dendrites were removed with laser surgery (left). The same cell was imaged at 48 hours and 96 hours after the dendrites were removed. At 48 hours (middle) a new dendrite arbor extends from the cell body, and by 96 hours the new arbor fills the entire space normally occupied by the cell. Credit: Rolls lab

Each step along the research pathway leads Rolls and her group to their long-term goal: use the basic knowledge of neuronal cell biology and neuronal responses to injury to improve outcomes in neurodegenerative disease and neuronal injury. With each research discovery, the team gains a better understanding of neuronal biology, which could someday be used in a practical application.


Mentoring Undergraduates in the Lab

While many labs at universities only employ faculty, graduate students, and research staff, the Rolls lab, and a number of others across the college, regularly invite and encourage undergraduates to participate in the lab work. At any given time, you can find about 10-15 undergraduate students either working alongside Rolls or doing their own independent research. Knowing that students need research in order to go to graduate school or to pursue a research-related occupation after college, Rolls opens her lab to students who are willing to make a commitment to research.  

“I really love working with undergraduate students in the lab if they are truly motivated about research,” Rolls said. “I believe in giving students the opportunity to work in the lab, along with the tools they need, and a research question to pursue, but ultimately it’s up to each student to succeed.”

The knack for research and discovery has been engrained in Rolls from a young age.
Both of her parents were Oxford researchers—her father Edmund in computational neuroscience and her mother Barbara in nutritional physiology.  Rolls had her own experience as a fledgling scientist participating in a research lab at a young age. As a high school student, she secured a spot in Carolyn Machamer’s cell biology lab at Johns Hopkins University, despite her age and inexperience. After that initial summer, Rolls was invited back for three more during her summer breaks as an undergraduate at Yale. Despite being young and inexperienced, Rolls was given a chance to prove herself, and did. Because of this, Rolls recognizes the need to give undergraduates an opportunity to make discoveries, develop a lab work ethic, and be successful as a researcher.

Rolls has also recognized the need to help change-of-location students obtain the research experience they need to apply for graduate school. She has been working with Carl Sillman, a senior lecturer in biochemistry and molecular biology, on a course that is offered for juniors including those who have just moved to University Park from a commonwealth campus or other university. “Students come to University Park as juniors and have not yet had the opportunity to participate in research. This makes it difficult for them to apply for a Ph.D. program because they are behind their University Park peers in lab participation,” Rolls said.

Rolls and Sillman give these students an opportunity to take the “fast track” into research by taking a class offered by Rolls that puts them in the lab immediately and teaches them how to answer questions in the lab. As with any undergraduate student doing research, they learn pretty quickly whether or not research is something they enjoy or loathe. “Research isn’t for everyone, but it’s important to provide the opportunity to experience it,” Rolls said.


Taking the Lead

When she’s not mentoring undergraduates or helping them integrate into her lab, Rolls wears several hats with graduate students, serving as the department’s graduate program liaison officer, working as an ombudsperson for students, and helping them with research in her lab.

Despite the time that going out of her way to work with students takes, Rolls still finds time to pursue another initiative, serving as founder and director of The Center for Cellular Dynamics.

“I started this in 2008 soon after I arrived at Penn State because I realized that there were a lot of people here with shared scientific interests, but it took me a long time to find them because they are scattered in different departments and colleges,” Rolls said.



Michelle Stone microscopeMichelle Stone at a confocal microscope equipped with a pulsed UV laser for severing fruit fly neurons, in the Rolls Lab. Credit: Seth Palmer

The center brings together scientists who study the cytoskeleton and intracellular transport, cellular changes during development and disease, cell-cell communication and interactions, and who use live imaging. This interdisciplinary group of faculty meets monthly to brainstorm science ideas. Additionally, Rolls helps center faculty organize workshops and mini-meetings throughout the year. Their most recent event, a workshop on a new genome engineering strategy that makes use of clustered regularly interspaced short palindromic repeats, included nearly 100 people from across campus. This type of interdisciplinary engagement and collaboration is one of the reasons that Rolls chose Penn State.  

“I wanted to come to Penn State for its research-centric community. The college and the Huck Institutes of the Life Sciences have been great for supporting interdisciplinary research,” Rolls said. “Being closer to my mother, who is a professor of nutritional sciences at Penn State, also enticed me to settle here.”

Penn State Science was a natural fit for Rolls. When Rolls was considering where to start her lab, she had a one-year-old and knew that she could only succeed in a place where the environment was supportive of families and children. After talking with other Penn State faculty and visiting the Bennett Family Center (the child care facility on campus), she knew that Penn State was the only place where she could juggle family, run a lab, teach, and have opportunities for leadership.

Rolls also has interests that extend beyond the lab and classroom. She has served as a chair and co-chair of the Eberly College of Science Climate and Diversity Committee for several years, where she helped guide the committee toward undertaking numerous climate-related initiatives.

“Melissa was a driving force in the distribution and display of the college Code of Mutual Respect and Cooperation and of the establishment of the digital signage now found in eight key locations in college buildings around campus,” said Chuck Fisher, professor of biology and co-chair of the committee. "Her energy and commitment to improving the climate for all members of the college, coupled with her considerate but aggressive approach with new projects, has been a major factor in the success of the committee for the past several years.”

In her seven years at Penn State, Rolls has been able to undertake and effectively manage an impressive number of initiatives. From establishing a successful lab, to mentoring students, to managing multiple leadership roles, Rolls has committed her energy towards making an impact and excelling everywhere she is involved. Although only time will tell what is on the horizon for her next big discovery or project, the college community is looking forward to seeing what Rolls sets out to accomplish next.