Biomedical Graduate Studies

Description of Research Expertise

The Logsdon laboratory uses long-read sequencing, innovative computational methods, and synthetic biology approaches to investigate the sequence and structure of regions of the human genome that have remained unresolved for the past two decades. We are particularly interested in the centromeres, which comprise over half of the previously unresolved sequences and are among the most dynamic and rapidly evolving regions in the human genome.

Completing the human genome
In 2001, scientists working on the Human Genome Project announced that they had finally completed the sequence of the human genome. However, 8% of the genome was never actually resolved. While a small portion of the missing sequences reside within segmental duplications (~2%), rDNA arrays (<1%), and telomeres (<<1%), the majority of missing sequences actually reside within our centromeres (~5%). Centromeres are essential chromosomal regions that mediate the segregation of chromosomes during cell division. They are composed of near-identical tandem repeats that can span up to several megabases on each chromosome. The repetitive nature and large size of these regions has hindered efforts to resolve their sequence using short-read sequencing, and consequently, all centromeres remained unresolved in the human reference genome. During her postdoctoral training, Dr. Logsdon developed long-read sequencing methods and novel computational approaches to generate the first complete sequence of a human autosomal centromere (on chromosome 8; Logsdon et al., Nature, 2021). This work led to the complete sequence of all human centromeres (Altemose, Logsdon et al., Science, 2022) and, ultimately, the completion of the human genome (Nurk et al., Science, 2022).

Our research
The complete sequence of each human centromere provides an unprecedented opportunity to determine their variation, evolution, and role in disease for the first time. As such, the Logsdon lab aims to uncover the genetic and epigenetic variation of centromeres among the human population and in diseased individuals, develop a model of human centromere variation, and use this model to study their basic biology and function. In addition, the Logsdon lab plans to reconstruct the evolutionary history of centromeres over the last 25 million years using phylogenetic and comparative approaches with both human and non-human primate species. Finally, the Logsdon lab will apply our discoveries of centromeres to design and engineer new ones on human artificial chromosomes (HACs). This effort will build on Dr. Logsdon's previous success in engineering HACs (Logsdon et al., Cell, 2019) and has the potential to revolutionize scientific research and medicine through the design of custom chromosomes and genomes. Together, our lab's research will advance our understanding of the complex biology of human centromeres and will generate HACs that have the potential to fundamentally transform scientific research and medicine.