RESEARCH GOALS
Our lab aims to boost human happiness through the lens of mitochondrial DNA (mtDNA). We study how mtDNA influences everything from human pregnancy to living a healthy and long life. To understand the role of mtDNA in humans, we analyze evolutionary diversity on a large scale, from tiny worms to large whales; this helps to uncover the main patterns that shape mtDNA evolution: mutagenesis, selection, and drift. With these insights, we aim to improve in vitro fertilization, diagnostics of mitochondrial diseases, characterization of somatic mutations in different tissues (cancer and healthy), and promote healthy aging, thus advancing the field of mitochondrial medicine.
RESEARCH DIRECTIONS
Evolution of the mitochondrial genome. We are interested in the evolution of the mitochondrial genome, a remnant of ancient bacteria integrated into our cells through symbiosis. This genome, frequently utilized by ecologists and taxonomists and encompassing the COX1 gene essential for the ‘barcoding of life’, has been extensively sequenced across hundreds of thousands of species. Leveraging this vast array of comparative species data on mtDNA, we use bioinformatics to dissect the evolution of mtDNA, which is based on two fundamental processes: mutagenesis and selection. Notably, by analyzing mtDNA from a diverse array of species, such as whales, naked mole rats, ostriches, penguins, hummingbirds, and others, we gain valuable insights into mtDNA dynamics in various human conditions, including cancers and diseases.
Embryology. As modern society increasingly shifts toward later-stage reproduction, we face challenges, including higher risks of genetic anomalies in embryos and infertility. In response, we collaborate with leading in vitro fertilization (IVF) clinics to create a comprehensive database of human embryo genomes and phenotypes. This resource provides researchers with invaluable data to identify genetic markers linked to successful pregnancies and childbirth. Our analysis uniquely positions us to identify critical genetic markers of embryonic viability. We aim to differentiate between embryos likely to develop healthily from those that may not thrive post-implantation. Currently, our focus is on the mitochondrial genome due to its vital role in energy metabolism, which is crucial for cellular function and development. Mitochondrial dysfunction can significantly impact fertility and reduce the chances of a successful pregnancy. Our objective is to decode mitochondrial mechanisms essential for fertilization, pregnancy, and childbirth. This effort aims to provide key insights into embryonic selection and improve our understanding of fertility, paving the way for innovative diagnostics and treatments. Our initial findings promise to significantly enhance the success rates of IVF treatments.
Selection of domesticated species. Historically, the domestication of wild species and artificial selection have aimed to enhance traits beneficial to humans, such as increased milk production and meat yield. However, this process has led to the disharmony in the molecular evolution of these species, resulting in the degradation of their genomes through the accumulation of slightly deleterious variants in traits not selected by humans. This has caused a decrease in fitness, marked by a lower health score, increased susceptibility to diseases, and reduced tolerance to environmental changes. Our goal is to improve the genome quality and, consequently, the health status of domesticated species while maintaining, and possibly also enhancing, the traits selected by humans. To achieve this, we are identifying strong stressful factors that induce truncating, purifying selection, where the majority of organisms burdened with an excess of slightly deleterious variants are eliminated, leaving behind the healthiest individuals in the population. Our initial experiments with the common carp, Cyprinus carpio, indicate that heat shock could serve as a universally applicable factor, selectively eliminating larvae with a high load of slightly deleterious variants. We are currently working to apply our genome purification method to other domesticated species, aiming to enhance their overall health and viability.
Mitochondrial component of healthy aging. We age due to the accumulation of errors that propagate in our tissues over time. In our lab, we focus on the mitochondrial component of aging, with a particular emphasis on mitochondrial DNA (mtDNA). mtDNA significantly influences aging, primarily due to two properties: (i) its fragility, evident from a mutation rate 100 times faster than nuclear DNA, and its susceptibility to long deletions; and (ii) its competitive nature at the intracellular level. Within each cell, multiple mtDNA copies compete, each replicating at different rates. This leads to ‘selfish’ selection, where mtDNA variants with rapid replication rates but lower functionality can dominate. Such scenarios are more prevalent in slowly dividing host cells, like neurons and skeletal muscles – exactly the tissues well-known for numerous ‘mtDNA problems’. We aim to unravel the factors that drive mtDNA mutagenesis (its fragility) and selection (competitive dynamics). By understanding and addressing these dual aspects of mtDNA – its mutagenesis and selection – our research seeks to illuminate the mitochondrial contributions to aging and develop strategies for healthier, longer lives.