Headshot of Lexy von Diezmann
Office Address

4-128 MCB
420 Washington Ave SE
Minneapolis, MN 55455
United States

Lab Address

MCB 4-180
420 Washington Ave SE
Minneapolis, MN 55455
United States

Lexy

von Diezmann

Assistant Professor
Genetics, Cell Biology and Development

Our lab studies how proteins self-organize and pattern cells from a quantitative, interdisciplinary perspective. We focus on how crossover repair is coordinated during meiosis in the model organism C. elegans.

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Research statement

Our lab’s mission is to understand how the random diffusion, interactions, and reactions of signaling molecules create emergent function and subcellular organization. We focus on the first moment of genetic distinction between parent(s) and progeny in sexual reproduction: recombination, or “crossing over,” between chromosomes during meiosis. To understand this process, we take an interdisciplinary approach, leveraging advanced microscopy, bioengineering, and mathematical modeling.

Each pair of parental chromosomes must form one or more physical linkages/genetic exchanges called crossovers to be correctly partitioned into haploid spores, eggs, or sperm. To accomplish this, meiotic nuclei deliberately induce DNA breaks at random sites throughout their genome, of which a subset are repaired via the crossover repair pathway. This process is tightly regulated to produce at least one crossover per pair of chromosomes. In what is termed crossover interference, when two or more crossovers form, they are more regularly spaced than would be expected from chance alone. However, while crossovers and interference were first described by classical genetics experiments in the 1910s, we are still working to identify the mechanism that coordinates DNA repair events separated by millions of base pairs.
   
To study the molecular basis for interference, we work in the model organism C. elegans. This small roundworm is transparent, genetically tractable, and produces eggs and/or sperm throughout its adult life. Critically, meiotic progression is easily visualized within its gonad: not only are its hundreds of developing gametocytes conveniently ordered by meiotic stage, but the proteins that bring together and that repair chromosomes can be resolved with light microscopy. By observing protein distributions – spatiotemporal and statistical – at each step of the crossover designation process, we build quantitative models of how DNA repair sites mature.
   
To understand how these nanoscale protein dynamics generate crossover interference, we introduced tracking of single fluorescently labeled proteins in live meiotic nuclei. We find that a key signaling protein of the crossover designation pathway diffuses along the liquid-like protein interface between chromosomes and is captured by mature repair intermediates. Simulations using these data suggest this behavior may be sufficient to produce crossover interference, but we have only scratched the surface.

Our current investigations focus on studying the dynamics of related proteins throughout the recombination pathway, defining the nature of the liquid-like environment between chromosomes, and developing technologies to repattern where and how many crossovers form. The insights gained from this work have the potential to restore human fertility at older ages, to improve our ability to generate new crops, and even to design new therapies for cancers including breast, prostate, and ovarian cancer that use the same pathway and are impacted by the same genes (e.g. BRCA1) as those that control meiotic break repair.

Selected publications

LvD, O. Rog, ‘Single-Molecule Tracking of Chromatin-Associated Proteins in the C. elegans Gonad,’ J. Phys. Chem. B 125, 6162-6170 (2021) [https://pubs.acs.org/doi/10.1021/acs.jpcb.1c03040]
   
LvD, O. Rog, ‘Let’s get physical: Mechanisms of crossover regulation,’ J. Cell Sci., 134, 1-12 (2021). [https://journals.biologists.com/jcs/article/134/10/jcs255745/268335/Let-s-get-physical-mechanisms-of-crossover]
   
LvD, Y. Shechtman, W.E. Moerner, ‘Three-dimensional localization of single molecules for super-resolution imaging and single-particle tracking,’ Chem. Rev., 117, 7244 (2017). [https://pubs.acs.org/doi/10.1021/acs.chemrev.6b00629]

Education and background

Education

  • 2018-2023 Fellow, Center for Cell and Genome Science, University of Utah, SLC UT
  • 2011-2018 PhD, Chemical Physics, Stanford University, Stanford CA
  • 2007-2011 BA, Chemistry, Reed College, Portland OR

Selected awards   

  • 2023-2025 Dale F. Frey award for Breakthrough Scientists, Damon Runyon Cancer Research Foundation
  • 2021-present Leading Edge Fellow
  • 2019-2023 Mark Foundation Fellow of the Damon Runyon Cancer Research Foundation