Project Background

A large fraction of all genomes, including the human genome, is composed of repeated sequences, which are challenging to study. To understand how repeated regions are organized and how they work, my research team studies a simple fungus found in almost every home across the globe: baker’s yeast. We have developed a novel technique called CheC-PLS: chromosome conformation by proximity labeling and long-read sequencing. CheC-PLS indelibly marks, and then decodes, regions in the genome that are associated with specific chromosomal factors or nuclear structures. We use a novel sequencing technology called Nanopore sequencing. Unlike conventional sequencing technologies that reveal the order of a few hundreds of bases - the building blocks our genome is made out of - Nanopore sequencing generates reads that are longer than 200,000 bases. We are able to identify sequences that interact with structures or proteins of interest using Nanopore sequencing. This helps us to reveal how the blueprint encoded in the genome is executed. In other words, how the numerous directives that are necessary for us to develop and function and that make each one of us unique. As a proof of principle, we used CheC-PLS to characterize the structure of the chromosome during sexual reproduction - the process that produces egg, sperm, pollen, and, in fungi, spores. Our approach revealed the organization of the chromosome as an array of loops, similar to a mop - a structure that is essential for fertility.

Student Role

The student will learn learn how to use and apply CheC-PLS to parts of the genome called heterochromatin. Crucial regions of the chromosome, such as centromeres and telomeres, are composed of heterochromatin. However, since heterochromatin is mostly composed of repetitive sequences, it is not accessible to conventional genomic techniques. To apply CheC-PLS to heterochromatin, the student will learn how to engineer appropriate yeast strains, validate them, and apply our novel genomic approach to them. Students will learn to hone their presentation skills and other professional skills offered by the program.

Student Learning Outcomes and Benefits

The student will learn to carry out independent research. Specific techniques include genome engineering in yeast, PCR, preparing DNA, sequencing DNA, growing yeast cells, isolating yeast nuclei. Potential research activities include analyzing genomic data, preparing sequencing libraries, performing Nanopore sequencing, and analyzing yeast cell by microscopy.

 

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