Joji Marie Yap Teves

Name: Joji Marie Yap Teves

Nationality: Philippines

Academic Background: MSc Molecular and Cell Biology (University of Arizona, Tucson AZ, USA)

Project Title: Dissecting the role of transcription-linked enhancers in the intestinal epithelium

Project Background: Transcription is a central process essential to living organisms including development, cell-cell communication and response to environmental stimuli. A cell’s identity is influenced by coordinated transcriptional control. This process is regulated in the chromatin inside the cell’s nucleus by the interplay of the transcription factors, RNA polymerase and the genomic elements such as promoters, enhancers and gene bodies. One model system to study transcription is the intestinal epithelium- a versatile organ that dynamically functions as a selective barrier for both nutrients and external toxins. Regular cellular turnovers in the epithelium is demonstrated by cellular differentiation from the stem cells residing in the intestinal crypt during cellular replenishment and tissue repair. Precisely how this is regulated at the chromatin and transcriptional level remains an important biological question.

Project Aim: The broader question of my PhD research would attempt to address on whether chromatin interactions, specifically contacts between enhancers and genes influence the process of transcription and consequently the transcriptional program of a cell. We address this question using a combination of classical molecular biology experiments and high-throughput genomics. Specifically, using classical molecular biology principles, we obtain the interacting regions of the three-dimensional chromatin and capture this information at a genome-wide level using high resolution DNA sequencing. From the DNA sequence dataset, we then use computational tools and data integration to build maps of interacting genomic regions, specifically between enhancers and their target genes during the process of transcription. And finally, we then validate the functional relevance of the enhancer regions by genomic perturbation and also to biologically infer their function by correlating their activity in intestinal organoid cultures. Knowing how the relevant transcriptional enhancer-gene interaction contributes to the mechanism of how cells transitions into another state, using the intestinal epithelium as a testbed system, may refine our general understanding of both homeostatic and impaired cellular transformations at the chromatin level. Furthermore, we can begin to ask on whether this mechanism is an intestinal specific phenomenon or a more generalized intrinsic code present in the chromatin of living cells.

Expected Outcome:  I envision the project to be a testbed in utilizing high-throughput DNA sequence datasets to figure out the hidden messages in the chromatin that can inform about a cell’s identity. If we establish a pattern of signatures that are commonly found in dysregulated cells of the intestinal epithelium, we can use this paradigm to other cell types and even possibly in publicly available patient-specific DNA sequences to dissect their role in the transcriptional identity of cells. 

Contact:  joji.teves@brick.ku.dk