Sigman Scholar award offers UCLA undergraduates with unique research opportunities at CART

(L-R): Jose Gonzalez and Jillian Melbourne

Undergraduate students at UCLA are offered a unique opportunity to participate in research with CART faculty. The CART Sigman Scholars Summer Program for UCLA undergraduate students is an 8-10 week summer research position in CART in which selected students are paired up with a CART faculty member and their lab. This program is designed to provide a rigorous, in-depth research experience for those interested in pursuing a career focused in autism spectrum disorder (ASD). Students may work in the fields of basic and clinical research ranging from genetics, psychology, psychiatry, neuroscience, and education. CART has awarded Jose Gonzalez and Jillian Melbourne as the CART Sigman Scholars for 2019.

Jose Gonzalez is a first-generation American and first-generation college student from central California. He is entering his senior year at UCLA and is majoring in Microbiology, Immunology, and Molecular Genetics. His Sigman Scholar research position worked under the mentorship of Dr. Daniel Geschwind and the Geschwind Lab. He started working with the Geschwind Lab in 2018 under the mentorship of post-doctoral student, Mita Nayernia, PhD. His Sigman Scholars project aimed to use a CRISPR/Cas9 based activation system to rescue functionality in ASD linked genes that require both copies for normal development. ASD is a neurodevelopmental disorder characterized by impaired social interaction and repetitive behaviors. The genetics of ASD is highly complex - multiple causative gene mutations may each play a contributing role leading to a unique broad spectrum of disabilities that vary amongst patients. Because of the contribution of many genes, much effort has been given to identify genes that are frequently mutated in ASD patients; we refer to these as high confidence ASD genes. One such gene is Chromodomain Helicase DNA-binding Protein 8 (CHD8). In normal development, both copies of the gene are required to produce the necessary amount of CHD8 protein which regulates cortical growth/development. ASD patients with a mutation in either copy will not produce the sufficient amount of CHD8 needed, a phenomenon known as haploinsufficiency. In addition to its vital role in neurodevelopment, CHD8 also regulates many other ASD-linked genes, thus studying and working to correct this mutation in CHD8 would greatly help in understanding ASD. The method in which we are attempting to correct CHD8 haploinsufficiency is a CRISPR/Cas9-based activation system. CRISPR/Cas9 is a gene editing tool first found in bacteria as antiviral protection. Since then its uses, accuracy, and efficiency have improved and increased. CRISPRa utilizes the targeting capabilities of CRISPR/Cas9 but does not edit the DNA. Instead, an effector protein is linked to Cas9 to activate gene expression. Jose hopes to use CRISPRa to rescue CHD8 expression levels in haploinsufficient CHD8 cells and in a mouse model as a proof of concept for its broader use as a therapy.

Jillian Melbourne is a UCLA undergraduate student entering her senior year and majoring in Neuroscience and minoring in English. Her Sigman Scholars research position worked under the mentorship of Dr. Emily Wood and Dr. Mirella Dapretto in the Dapretto Lab. As an adolescent, Jillian volunteered with disadvantaged youth and came to meet a boy with Juvenile Batten Disease. During her experience volunteering, she worked with him to develop a relationship and broaden his social and communication skills, an experience which had a lasting effect on her. Jillian’s Sigman Scholar project examined post-traumatic stress disorder (PTSD) and ASD. Among the different comorbidities associated with ASD, PTSD has been given relatively little attention despite evidence that people with ASD may be more vulnerable and likely to experience trauma or early life adversity. Studies suggest that children with ASD are more susceptible to experiencing interpersonal trauma because of deficits in communication and emotional expression skills and are more prone to exposure to traumatic childhood events, physical and sexual abuse, and bullying when compared to typically developing peers. The goal of this project is to further examine the comorbidity rate of PTSD and ASD using data collected through the Adolescent Brain Cognitive Development (ABCD) Study. She also examined functional magnetic resonance imaging (fMRI) scans from this dataset, focusing on areas of interest in trauma, ASD, and sensory over-responsivity.