Colin Florian began their scientific career in 2014 when they became employed at the Genome Engineering and iPSC Center (GEiC) at Washington University in St. Louis. The focus of the GEiC is to generate genetically modified cell lines and animal models using the CRISPR-Cas9 system. In their time as a technician at the GEiC, they were able to master many molecular biology and tissue culture techniques as well as gaining computational experience. Additionally, they trained and mentored several new members of the team throughout my time spent at the GEiC.
Currently, Florian is a third-year molecular genetics and genomics graduate student in the lab of Joseph Dougherty at Washington University in St. Louis. Their research is focused on understanding how sequence composition influences transcription at genomic targets bound by Mmelin transcription factor 1-like (MYT1L), which is associated with neurodevelopmental disorders and autism when loss of function mutations are present. To address this question, they will be employing Massively Parallel Reporter Assays (MPRA) to test a multitude of MYT1L promoter targets. Through this research, Florian hopes to be able to identify and characterize mechanisms through which MYT1L functions to produce a transcriptional response.
Principal Investigator: Joseph Dougherty
Fellow: Shirley Lopez De Leon
Undergraduate Fellow Project:
Mutations in the gene myelin transcription factor 1-like (MYT1L) are associated with neurodevelopmental disorders and autism. It is an integral component for the generation of mature and functional neurons in vivo (see Chen et al., 2021; Wöhr et al., 2022). Furthermore, MYT1L loss of function mice show a sex x genotype interaction in transcriptional and behavioral responses (see Chen et al., 2021).
This project will specifically focus on transcription regulation by MYT1L. It is unknown why losing one copy of MYT1L results in disorder. This result suggest the hypothesis that MYT1L’s function in gene regulation depends on its level. Therefore, the SURFiN fellow will generate select MYT1L reporter constructs using a new cloning strategy being implemented in our lab. (This strategy will allow for inclusion of larger regulatory elements for reporter libraries which is traditionally restricted by synthesis and will benefit our lab as a whole). Several quality control checks provide data visualization for immediate confirmation and feedback of success. Once generated, these reporters will be functionally validated and tested in cell culture models. The fellow will then test the role of different levels of MYT1L protein on regulating gene expression using these reporters.
In summary, this project will provide the fellow with training and experience in literature review, molecular biology and tissue culture techniques, and data analysis with several checkpoints to provide affirmation and feedback.