Yale Child Study Center, New Haven, CT
As I began thinking about the types of programs I was hoping to participate in this summer, I knew one thing for certain: I wanted to become involved in research focusing on Autism Spectrum Disorder. This may seem like an incredibly specific area of interest, but having a younger brother with ASD, and having gained such a strong understanding of the effects the disorder can have on the individual as well as their family and friends, I felt compelled to find a position that would allow me to better understand where ASD and other neurodevelopmental disorders arise from. More importantly, I hoped to contribute to research that worked toward therapeutic agents or programs to help mitigate the intellectual, behavioral, and physical challenges faced by some individuals with ASD. At the same time, as my ultimate goal is to become a physician, I was also searching for a way to grow and gain experience in the field of medicine.
The Developmental Science Summer Internship at the Yale Child Study Center offered me the incredible opportunity to meet all of these goals. As an intern in this program, I was matched with a faculty member whose lab work was congruent with my own interests: Dr. Ellen Hoffman’s research focuses on the presentation of behavioral phenotypes in zebrafish resulting from mutations in genes that have been identified as ASD risk genes, with the ultimate goal of identifying compounds that might have therapeutic effects on these behaviors. My work in her lab consisted of characterizing these alterations in specific behaviors in zebrafish mutated for three high-confidence ASD risk genes: chd8, grin2b, and katnal2. These genes were identified as having loss-of-function de novo mutations in individuals with ASD through the use of whole-genome sequencing, though the incidence of de novo mutations in any one gene is still quite rare. It may be difficult to understand the relevance of characterizing behavioral changes in zebrafish in order to characterize a human disorder at first glance. Because Dr. Hoffman’s work focuses on defining behavioral phenotypes and working backwards in order to determine what neural circuits may be affected, her research allows for a more exploratory approach to determine how specific genes may affect brain development in humans. Also, because it involves isolating and characterizing the effects of individual ASD risk genes, this research may allow for more targeted treatment approaches based on the specific mutations any given patient possesses. Because ASD has such a heterogeneous presentation, this type of approach is highly relevant for the creation of therapies tailored to specific deficits.
Specifically, my research project involved identifying change in activity in response to startle and overall activity during restful and wakeful periods in zebrafish mutant for one of these three risk genes. In order to accurately and reliably characterize the effects of a given gene on behavior, I first had to raise zebrafish to the developmental stage at which the affected gene is most highly expressed. To do this, I set fish that possessed a given mutation to breed, and collected embryos to grow for five days. These larvae were then tested for their behavioral responses to visual startle and their resting and waking activity by using computer software to track their movements in a defined space, and were genotyped in order to determine whether they possessed a fully loss of function mutation (homozygous), only one copy of the mutation (heterozygous) or were wild-type for the mutation. In this way, it was possible to categorize the activity of each fish based on their genotype, and then to compare the activity profiles of the mutant fish against wild-type fish to determine whether any differences could be reliably observed. My experience in Dr. Hoffman’s lab challenged me to learn new skills and laboratory procedures, and more importantly, taught me the kind of care, patience, and perseverance required to be successful in a research environment. This experience also required me to delve deeply into my research, understanding the roles of different ASD risk genes in neurodevelopment in order to present my research to other researchers at the Child Study Center at the end of the program. As I strove to truly understand the intricacies of the research and effectively explain my work, I gained skills that will allow me to become a more dedicated student, a more successful researcher and a more effective teacher and communicator. These are skills that I hope to carry forward in my time at Williams as well as in future work.
While the majority of my time in this program was taken up performing experiments and analyzing data in Dr. Hoffman’s lab, I was also able to attend talks led by students in the neuroscience MD/Ph.D. program at Yale, which allowed me to better understand what avenues of research exist in the field of neuroscience, as well as how research can be incorporated into a medical profession. As my ultimate goal is to enter into the medical field, I found the opportunity to get a glimpse of this area of medicine highly valuable. I was also able to attend meetings between my lab and three other labs in the psychology and genetics departments within the Child Study Center, at which researchers were able to present ongoing work and discuss possible interpretations of new data. My participation in the Developmental Science Summer Internship also allowed me the opportunity to attend lectures each week given by faculty members at the Child Study Center whose work spanned a variety of fields within the overall discipline of developmental science and public health, touching on substance abuse, family development, adolescent neurodevelopment, and injury epidemiology among other topics. Having attended these lectures, we were then able to attend weekly meetings led by a group of interns who facilitated discussions and, in a third meeting, describe the research they were involved in. All of these meetings allowed me to better understand the collaborative, exploratory nature of research while exposing me to the wide variety of disciplines encompassed by neuroscience and developmental science research. In this way, though these experiences were not ones I expected upon entering into my internship, they were incredibly important for developing my understanding of and interest in research.
I feel incredibly fortunate to have had the opportunity to participate in the Developmental Science Summer Internship program at the Yale Child Study Center this summer. This experience allowed me to better understand not only the breadth of research being performed both at Yale and around the world in the fields of neuroscience and developmental science, but also the experience of performing research as a collaborative, intensive, and exploratory process. Even more importantly, I was able to work with such intelligent, encouraging, and supportive individuals during my time in this program, which only fostered my interest in and understanding of the nature of research. This experience and the skills I gained from it will certainly serve me well in my remaining time at Williams and beyond, and I am incredibly grateful to the ’68 Center for Career Exploration and the Class of 1972 Internship Program for sponsoring the grant that allowed me to take part in this program. I look forward to taking the skills and experience I gained this summer and incorporating them into my future endeavors as I continue to pursue a future in medicine.