Raise the Roof for Rett - October 28, 2016
This is an exciting year for the
SUKI FOUNDATION FOR RETT SYNDROME
AS IT MARKS THE 5TH ANNUAL
RAISE THE ROOF FOR RETT!
OCTOBER 28, 2016
Neuroscience trainees navigate challenges beyond the lab
Even though she possessed a bachelor’s degree in chemistry and a master’s in biotechnology, Lillian Brady felt that she didn’t fit into the booming field of neuroscience. “As an underrepresented student, it can be easy to get into the mind frame that you don’t belong,” says Brady, a graduate of Alcorn State University, a historically black university in southwest Mississippi.
Each Roadmap Scholar works closely with a research mentor. Here, scholar Lillian Brady (right) meets with neurobiology associate professor Lynn Dobrunz.
But then the Jackson, Mississippi, native found a place where she fit in perfectly: UAB’s Neuroscience Roadmap Scholars program, which is designed to help engage and retain underrepresented graduate trainees—including ethnic minorities and students with disabilities—in the neuroscience workforce.
Brady, now a doctoral student in UAB’s Department of Neurobiology, calls the program a “confidence booster” that has provided both support and encouragement. “I’ve been exposed to scientists who look like me and who have had some of the same challenges I am facing now,” she says. “These scientists are thriving in their fields, so I have no doubt that I can be successful in whatever career path I choose.”
Strengthening the Pipeline“Through our experience working with students, we realized the pipeline for diverse neuroscientists was leaky,” recalls Farah Lubin, Ph.D., associate professor of neurobiology. “We might start with many diverse, motivated students, but somehow, many of them don’t make it into successful careers.”
The problem isn’t talent or academic strength; rather, many students from diverse backgrounds or with disabilities may struggle with financial challenges, family needs, or a lack of confidence. Lubin and Lori McMahon, Ph.D., UAB Graduate School dean and UAB Comprehensive Neuroscience Center director, have seen such roadblocks dismantle the plans and goals of numerous students and coworkers.
Roadmap co-directors Lori McMahon (left) and Farah Lubin (right) serve as career coaches for scholars outside the lab.
To plug the pipeline’s holes, Lubin and McMahon developed Roadmap Scholars to emphasize mentoring, support networks, team-building experiences, and a community of peers to help guide more students to achieve neuroscience careers. Funded by a grant from the National Institute of Neurological Disorders and Stroke, the program launched in 2014. Today it includes 25 doctoral students.
The funding does not pay tuition or stipends; instead, it enhances and provides educational experiences to prepare students for further study and to encourage them to remain in neuroscience. And it works in tandem with the students’ graduate curriculum. For example, every Roadmap Scholar matches with a “career coach” in addition to a primary research mentor. The coach is a faculty member not on the student’s thesis committee who is available to talk about nearly anything—scientific projects, publishing and presenting, conflict management, or life in general, Lubin says. In doing so, these coaches provide additional professional perspectives and serve as an additional layer of support.
For Leland Fleming, a Fort Worth, Texas, native and UAB Graduate Biomedical Sciences doctoral student, the program’s peer and faculty network has made his goal of becoming a neuroscientist more tangible. “With its guidance and inspiration, it has made a once seemingly impossible goal something that I feel more than capable of accomplishing,” he says.
Leland Fleming (right) with his research mentor, neurobiology assistant professor Kristina Visscher
Creating a CommunityThe support system kicks into gear even before the scholars’ first semester at the program’s summer NEURAL (National Enhancement of Underrepresented Academic Leaders) Conference, which draws neuroscience trainees from across the country. There, students can hone their networking and public speaking skills and interact with the field’s academic leaders. For instance, at the 2015 inaugural conference, leading neuroscientist Roger Nicoll, M.D., of the University of California San Francisco drew an emotional response from the audience when he spoke of succeeding despite his lifelong struggle with dyslexia.
For Fleming, key conference takeaways included insights on common challenges that minority students can face in graduate school. These might be “feelings of inadequacy or feelings that he or she is merely an impostor on the brink of being exposed at any given moment,” he explains. But he and other students also received “terrific advice on coping with these issues when they arise,” Fleming says.
Lubin serves as a research mentor for scholar Rylie Hightower (right).
The conference also helps to build strong bonds among students. Matthew Timberlake, a second-year graduate student who grew up in Fort Worth and Enterprise, Alabama, has enjoyed helping his colleagues to design and present lectures—even sharing his own research data with them. “I like the sense of community,” he says. “My colleagues and I—especially the upperclassmen—have an important role in discussions,” he says. “We help to ease some of the unknown for the underclassmen. In the same way, I also benefit from the upperclassmen’s advice and guidance.”
Rylie Hightower, an Albuquerque native who came to UAB after earning a nursing degree in New Mexico, is one of the newer students benefiting from those discussions. At a Roadmap spring retreat, Hightower sought advice from older students. Those interactions “will help me throughout my time at UAB and beyond,” she says.
The program has “made me feel at home away from home,” Hightower says. “But it also has helped me understand that a supportive community can greatly contribute to the way I think and perform as a student and as a scientist.”
Matthew Timberlake works with research mentor and psychiatry professor Yogesh Dwivedi.
The Road AheadCareer planning is a key component of the program. Brady, who plans to obtain a postdoctoral position following her UAB training, found Roadmap’s “postdoctoral school” to be extremely valuable. She describes it as a weeklong crash course for senior graduate students covering “everything we need to know about postdoctoral positions. Not only were we given pointers on securing the right postdoc for our interest, but we also were exposed to postdocs in fields we might not have considered.”
Every student also learns about neuroscience-related job opportunities in business and industry. “Often, students are encouraged to build a career path focused on remaining in academia,” says Megan Rich, a Fairfield, Connecticut, native and UAB Graduate Biomedical Sciences student. “The program has been great about expressing other options after graduate school and that it is OK to think about them.”
By helping these students to feel empowered, capable, and supported, the Neuroscience Roadmap Scholars program will lay the groundwork for future progress in one of the fastest growing scientific fields, McMahon says. Lubin agrees, noting that diversity is crucial for continuing advancements: “Diverse groups can offer unique perspectives and unique ideas, which will push the field forward.”
• Learn more about the Neuroscience Roadmap Scholars Program, including how to apply.
• Give something and change everything for the next generation of neuroscientists by supporting the School of Medicine.
Published October 2016
Emerging Scholar Year-End Report - Jessica Nichols
Mild traumatic brain injury (mTBI) accounts for the majority (75%) of the 2.5 million brain injuries estimated to occur in the United States each year. Individuals that acquire a mTBI can experience a range of complications including cognitive deficits, sleep disturbances, and neuropsychiatric changes, with repeated mTBIs (rmTBI) resulting in a worse prognosis. Utilizing a clinically relevant mouse model of mTBI and rmTBI, I was able to recapitulate some of functional alterations experienced by the human population. My data reveled that while sustaining a single mTBI results in slight and acute impairments, mice receiving repeated mTBIs experience more robust and longer lasting deficits in learning and memory, sleep disturbances, and lack of motivation to perform activities of daily living. This mouse model was used in my subsequent studies and will be used in future research to evaluate injury mechanisms and therapeutics.
Following initial insult to the brain, alterations in the neurochemical, cellular, and metabolic environment occur which elicit a secondary injury cascade and ultimately lead to the functional deficits described previously. Neuroinflammation plays a key role in secondary injury, with the activation of transcription factor nuclear factor kappa B (NF-κB) and an increase in production of reactive species being two contributing factors. I investigated the efficacy of a drug, a catalytic oxidoreductant, in targeting these factors and thereby reducing inflammation post-rmTBI. My research demonstrated that drug administration post-rmTBI could decrease reactive species and NF-κB activation acutely and sub-acutely after injury. Current studies are looking at additional markers to determine the inflammatory state of the mouse brain post-rmTBI and drug administration; while, future studies plan to evaluate the effect of this drug on functional outcome.
After a single mTBI, 80-90% of individuals recover in approximately 1 week without intervention. The same does not hold true for repeated mTBIs. One aspect of my research sought to explore the mechanism behind this spontaneous recovery. Utilizing a transgenic mouse line with selectively labelled newborn granule cells, I evaluated the effect of mTBI and rmTBI on neurogenesis. No significant differences between groups were observed when I looked at the number of newborn neurons. However, future experiments plan to examine neurogenesis further by looking at how these newborn neurons are integrating into the CNS circuitry to determine if there are differences which could be contributing to the functional impairments seen after rmTBIs.
Emerging Scholar Year-End Report - Jada Vaden
The extensive synaptic networks between neurons allow information to flow throughout the brain, enabling consciousness, perception, movement, and learning. Breakdown of this transfer of information contributes to complex neurodevelopmental disorders ranging from autism to schizophrenia. Understanding the factors that enable reliable communication between neurons is therefore a critical goal of neuroscience.
Synaptic transmission occurs when an action potential invades a presynaptic terminal and causes the release of a vesicle of neurotransmitter. The neurotransmitter then binds to receptors in the postsynaptic cell, causing an electrical signal. It was believed, until fairly recently, that a presynaptic terminal could release, at most, one vesicle per action potential, and that the probability that any vesicles would be released was fairly low. However, evidence is mounting that a single terminal can release multiple vesicles under some circumstances. This process, termed multivesicular release (MVR), greatly enhances the reliability of neuronal communication, but the molecular events that allow it to occur remain unknown.
I investigated this question at the synapse between the climbing fiber and Purkinje cell in the cerebellar cortex. Previous work has established that MVR is prominent at this synapse; in fact, a single presynaptic terminal is thought to release 3-5 vesicles per action potential. My initial experiments suggested that protein kinase A (PKA), a molecular machine that modifies the activity of other proteins, was prominent at this synapse, so I asked whether PKA contributes to MVR. In my experiments, activating PKA increased MVR and, conversely, inhibiting PKA decreased MVR.
Because PKA regulates the activity of other proteins, the next challenge was to identify which of PKA’s targets is critical for MVR. I did this by testing whether activation of PKA still increased MVR in mice lacking the genes for various PKA targets. The prediction was that, in a mouse lacking PKA’s primary MVR-stimulating target, PKA activation would no longer enhance MVR. After performing these experiments in several lines of mice, I found that PKA activation did not enhance MVR in mice lacking the gene for synapsin. This suggests that PKA stimulates MVR by modifying the activity of synapsin. Moreover, because mutations in synapsin have been identified in human patients with autism, my results may shed some light on the deficits in neuronal communication observed in this disorder.
Ongoing experiments are focused on uncovering the mechanism by which PKA and synapsin increase MVR. Specifically, I’m testing whether activation of PKA increases the probability that a vesicle of neurotransmitter is released in response to an action potential or, instead, increases the number of vesicles available for release. While preliminary results support the latter explanation, I have planned several additional experiments to strengthen this conclusion.
The Whit Mallory Fellowship has been instrumental in my progress during the past year. Funds from the fellowship allowed me to obtain genetically modified mice and the mission of Civitan International inspired me to choose PKA targets that had previously been implicated in intellectual disorders. The fellowship also allowed me to visit a lab at the University of Texas to learn a new surgical technique and travel to a premier conference to present my results. Discussions with leading scientists at this conference helped me to design experiments to better understand the mechanism by which PKA increases MVR. Finally, I have been able to hire two talented pre-med students to assist with these experiments. The time they spend in lab will help to further my research, prepare them for success in medical school, and allow me to hone my mentoring abilities for the next step in my career.