Libuda Lab | Research

The Libuda Lab studies how DNA is accurately repaired during sperm and egg development.

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Live imaging of germ cell chromosome structures in whole intact C. elegans

How is the genome faithfully passed on through generations?

Utilizing molecular genetics, live and fixed imaging, super-resolution and high-resolution microscopy, CRISPR-Cas9 genome engineering, genomics, and biochemistry, the Libuda lab studies the molecular mechanisms behind how DNA double strand breaks (DSBs) are made and repaired during sperm and egg development to ensure genomic integrity and accurate chromosome segregation through generations.

Superresolution imaging of meiotic chromosome structures

Specifically, we study DSB formation and repair during meiosis, the specialized cell division that generates sperm and eggs. For our studies, we use two model organisms that have strong conservation with human fertility processes: the nematode Caenorhabditis elegans and the zebrafish Danio rerio. Our work has strong biomedical relevance for understanding fertility issues, birth defects, and cancer.

Some of our current research interests include:

Molecular mechanisms of DNA repair pathway choice

While repair of DSBs with the appropriate chromosome template (homolog) is necessary for genomic integrity in germ cells, very little is known as to how germ cells achieve this repair template preference in the presence of other potential templates with nearly identical sequences (sister chromatids).

defective segregation of meiotic chromosomes (green) with excess crossovers

How do specific chromosome structures regulate and respond to DNA repair pathway choices?
How and when are mitotic DNA repair pathways engaged during meiosis? Are there consequences to using these pathways during germ cell development?
How does chromosomal context (or location) of DSBs affect how and when it is repaired?
What sexual dimorphisms exist for DSB formation and repair? What generates those differences?
Identification of novel regulatory proteins using genetic screens
Whole genome analyses of DNA repair landscapes
What are the dynamics of DSBs during repair? How do the kinetics of repair impact repair pathway choices?
Developing and utilizing novel reagents and techniques to detect and analyze DNA repair outcomes

Genomic analysis of crossovers

Heat-induced male infertility

In multiple organisms from plants to humans, male fertility is acutely sensitive to changes in temperature. Our research found that acute heat shock activates mobile DNA elements, called transposons, only in developing sperm. We are uncovering the molecular mechanisms behind why only spermatogenesis is affected.

heat-induced DSBs (green) in single spermatocyte

What sexual dimorphisms contribute to heat-induced male infertility and protect oogenesis?
How does heat-induced DNA damage get repaired?
Evolution and conservation of temperature-induced male infertility mechanisms