Informace o projektu

Anotace je dostupná pouze v anglickém jazyce.

Understanding how genetic and epigenetic variation in the most complex, i.e. repetitive, parts of the human genome affects health and disease is central to my research. Until now, genetic research only focused on a small known number of medically relevant genes, and a single reference human genome was used for all of humankind. We now know that such reference inaccurately represents complex parts of the genome, and completely misses others (such as telomeres, approximately half of the chromosome Y, centromeres, or satellite-rich parts of acrocentric chromosomes). Notably, these regions can now be resolved with long-read assemblies that are of higher quality than the previous single human reference used by all the researchers. We can now study the telomere length of single molecules for individual chromosomes, the full length of the Y chromosome, the complete and accurate sequences of centromeres and acrocentric chromosomes, as well as all single nucleotide and structural variants with base error rates as low as one error per million basepairs. In my future research group, we are especially interested in four questions: 1) What factors determine telomere length and how does it change with age and cancer progression? 2) To what extent is the Y chromosome lost in cancer and how does it affect the prognosis? 3) What genetic and epigenetic variants in centromeres are associated with aneuploidies, particularly on sex chromosomes? 4) How does repetitive DNA on human acrocentric chromosomes predispose genomes to various translocations (i.e. Robertsonian translocations)? I have the expertise, experience, and ambition to address the above-mentioned biological questions using the latest genomics technologies, including the latest nanopore sequencing with high accuracy and inherent methylation profiles that enable us to study all of the human genome, telomere-to-telomere, and uncover biological processes previously hidden in vast arrays of repetitive DNA. I also have an established research network with several world-leading experts, including my postdoctoral supervisor and the co-founder of the Telomere-To-Telomere consortium, Associate Prof. Karen Miga. The collaborative environment of Masaryk University supplemented by MASH StG/CoG funding would accelerate the discovery process and bring us closer to the ultimate goal of personalized genomics for everyone.