Dr. Andrea Gomez
Assistant Professor UC Berkeley
Postdoctoral Fellow University of Basel, Switzerland
PhD in Developmental Genetics New York University
Dr. Andrea Gomez saw the perfect opportunity to delve into her recent fascination with red blood cells when a classmate’s nose began to bleed during elementary school. Much to her teacher’s horror, Andrea swirled the pooling blood around with a stick, hunting for the tiny red blood cells she had recently learned comprised the liquid. Andrea learned two things from this – teachers don’t approve of impromptu science experiments involving blood, and red blood cells aren’t visible to the naked eye. This was Andrea’s modus operandus as a child; she was fascinated by the invisible elements that compose living things. As a professor of Cellular and Molecular Biology at the Helen Wills Neuroscience Institute of UC Berkeley, Andrea remains fascinated by the tiny building blocks of biology and has focused in particularly on the study of RNA. Now, she is equipped with upgraded investigative tools – a microscope, and her own lab!
Andrea’s first experience in research was during a summer workshop focused on medicinal plants at New Mexico State University. As part of the workshop, she was tasked with performing titrations and high-performance liquid chromatography (HPLC), a method used to determine the components of a mixture. Andrea found the experience romantic – not knowing the exact processes behind the methods made them mysterious and exciting, and she was excited to play a role in scientific research.
Despite her summer romance with HPLC, Andrea was still deciding whether she would pursue a research career. As she began her Bachelor's degree at Colorado State University, she still “had flirtations with doing medicine.” An unfortunate grade on an anatomy test left her more resolute; she decided to focus on researching biological mechanisms, not on the memorization required in medicine. While in college, Andrea worked in both an avian physiology lab and a crustacean endocrinology lab. As she continued to learn more about many different organisms and their unique evolutionary traits, she decided she wanted to study evolution and the genetic code that underlies it in graduate school.
As an undergraduate, Andrea had the opportunity to attend a conference for the Society for Advancement of Chicanos/Hispanics & Native Americans in Science (SACNAS). At their career fair, her interest was piqued by an indigenous woman at the NYU booth who was advertising their indigenous club. Thrilled by the idea of finding a native community in graduate school, Andrea applied and was accepted to the NYU PhD program in developmental genetics. Upon arrival at NYU, Andrea discovered she was one of the first native PhD students in her program. Despite this, she still found a thriving native community across other disciplines at the university.
As a PhD student in the lab of Dr. Steven Burden, Andrea was interested in studying how synapses develop. She joined a lab focused on a particular synapse: the neuromuscular junction, which connects muscles and motor neurons. She studied a protein called LRP4, which signals from its location on the muscle synapse that a neighboring motor neuron should stop growing and make a connection – a process used for creating muscle-neuron connections during development. Andrea wanted to understand how the protein performed this signaling between the pre- and post-synaptic sides. She suspected that the intracellular part of the protein may be involved; it could communicate signals from inside the muscle cell to the external surface, and thus the motor neuron. However, at the end of her third year, Andrea discovered that this intracellular part of the protein was not critical to the role of LRP4.
Andrea was unsure how to move forward after this disappointing result. Although Andrea was sure she wanted to become a scientist, she began to feel uncertain about her ability to “make it” in the academic world. However, Andrea was reminded of what she loved most about her early research experiences: following her own curiosity, as opposed to seeking validation from others. With this new perspective, Andrea decided to pursue a new question that had arisen naturally out of her original project. She had developed a conditional LRP4 knockout mouse in which LRP4 was still present in muscles (because lack of muscular LRP4 is lethal), but nowhere else. This gave her the opportunity to ask what LRP4 was doing in other, non-muscular cell types: for instance, in the brain. A neighboring PI, Dr. Robert Froemke, suggested she build an electrophysiology rig to see how the electrical properties of the neurons in mice without LRP4 in their brains differed from typical mice. She concluded that mice lacking LRP4 had fewer synapses, so neuronal input could not reach a necessary threshold for inducing synaptic plasticity, or the changes in neuronal structure and firing that occur in response to neuronal input.
Andrea’s PhD work focused on how one protein caused changes in synaptic complexity. For her post-doctoral work in the lab of Dr. Peter Scheiffele at the University of Basel, she wanted to take a step back. Andrea hoped to understand how complexity is produced not at the protein level, but at the level of genes. Intriguingly, both humans and mice have the same number of protein-coding genes – about 20,000. Andrea wondered: how does the same number of genes produce the mouse brain and the more complex human brain? One possible explanation is called RNA alternative splicing. A single gene contains many sub-blocks, called exons and introns. These blocks can be included or excluded when a gene is transcribed into messenger RNA (mRNA), creating many different possible mRNA isoforms, and thus proteins, from the same gene. This adds another layer of complexity to the genome. The amount of splicing that happens in neurons is highest in primates compared to all other mammals (and is relatively high in octopuses too)! This suggests the amount of splicing and brain complexity are correlated. In her post-doctoral work, Andrea hoped to understand how these isoforms may affect brain complexity. She focused on neurexin, a gene which has several isoforms known to affect synaptic organization. Andrea found that SLM2, an RNA-binding protein, was controlling the expression of different neurexin isoforms, and subsequently modulating synaptic plasticity.
Andrea began her lab in January 2020 at UC Berkeley, planning to continue in a similar vein to her post-doctoral work. However, the mouse models she needed were in Dr. Scheiffele’s lab – in Switzerland. When COVID shut down international flights, Andrea was unable to ship her mice, which meant many of her planned experiments weren’t possible. Around this time, a clinician at UCSF emailed her suggesting that they co-write a grant studying the role of psilocybin in cognitive flexibility. Although the grant was not funded, Andrea became so interested in the subject matter that she decided to get involved in psychedelics research at the conveniently located UC Berkeley Center for the Science of Psychedelics! Now, Andrea uses psychedelics as a model to understand how plasticity works. Psychedelics induce plasticity through a specific compound. Because of this, it may be easier to understand mechanistically how psychedelics induce plasticity in a controlled setting compared to environmental paradigms which are less constrained and harder to control for. Andrea hopes to understand how splicing and transcription are affected by psychedelic-induced plasticity. If we understood psychedelic-induced plasticity at the transcriptional level, we could mimic the effects of psychedelic-induced plasticity without using the drug itself. This application is especially germane in clinical situations where psychedelics are unsafe or ineffective but inducing synaptic plasticity may still be beneficial for patients, such as those with schizoaffective disorders or chronic conditions like neurodegeneration. As excited as Andrea is to harness the utility of psychedelics, she is equally passionate about engaging in equity and reciprocity with the indigenous communities that have acted as stewards of many of these substances for millennia.
From plasticity to alternative splicing, Andrea investigates how an ability to take many forms and adjust to the needs of an environment is crucial to building complexity in the natural world. Fittingly, Andrea herself is also remarkably nimble. From becoming an electrophysiologist in the 4th year of her PhD to switching to psychedelic research while starting her new lab, Andrea’s “pivoting skillset”, as she describes it, is a hallmark of her willingness to follow her curiosity, take risks and try new things to answer the questions she is interested in. Andrea’s unfettered curiosity will surely continue to guide Andrea and her lab in their study of how nature herself creates this adaptability within the building blocks of our synapses.
Find out more about Andrea and her lab’s research here.
Listen to Megan’s full interview with Andrea on September 6th, 2022 below!
