PIPages
Labs

Nancy E Kleckner

Harvard University, MA·Genetics

Chromosomes are often pictured as static bundles of DNA. This research instead treats them as "living, breathing objects" whose movements and shape changes in time and space make their functions possible.

Fields

Genetics

Biology

Biophysics

Topics

chromosome biology

meiosis

mitosis

Grants
1 known grant, through May 2030

What they work on

  1. Explore recombination-mediated chromosome pairing in budding yeast using 4D low signal-to-noise tracking of locus-specific fluorescent spots, and map global pairing patterns in Sordaria with live imaging and Expansion Microscopy.
  2. Test whether mechanical stress along chromosome axes sets crossover spacing by checking whether stress-related axis kinks (perversions) in Sordaria change in mutants with altered crossover interference.
  3. Test whether mutations in the HEAT repeat of the phosphatase PP2A, predicted to alter mechanical stress sensing, affect crossover interference in yeast.
  4. Develop nanoscale fluorescent sensors to map stress patterns on mitotic chromosomes in living cells, and test whether chromatin status shapes axis perversions.
  5. Use 4D imaging of walled E. coli and membrane-enclosed L-forms to test whether sister chromosome segregation limits division and whether nucleoid-membrane tension links the chromosome and cell cycles.

More about the research

It compares three settings: chromosomes in meiosis, the cell division that makes eggs and sperm; chromosomes in mitosis, ordinary cell division; and the nucleoid, the compact chromosome of the bacterium E. coli. Comparing them may reveal shared principles. A recurring idea is that mechanical stress along chromosomes helps organize what they do.

Why it matters

Errors in meiosis can cause infertility and birth defects, and faulty chromosome organization and segregation in mammalian cells underlie cancer. Bacteria use the L-form lifestyle to evade antibiotics. Understanding how chromosomes are organized and move could therefore inform research on fertility, cancer and antibiotic resistance.

Known grants

From NIH and NSF research grants. Labs often have other funding we can't see.

Chromosome organization and function in time and space: meiosis, mitosis and E. coli

NIH · May 2020 – May 2030

Closest labs

Amy MacQueen

Wesleyan University, CT·Genetics

Define how the N terminus of Zip1, a synaptonemal complex building block, works with the Zip3 SUMO ligase to promote crossover recombination in budding yeast, using structure-function genetic analysis.

Anne M Villeneuve

Stanford University, CA·Genetics

Uncover the mechanisms that ensure every chromosome pair forms a crossover, an exchange that links matching chromosomes so they separate correctly, in C. elegans meiosis.

Soni Lacefield

Dartmouth College, NH·Genetics

Adapt HyperTRIBE, which tags an RNA-binding protein so it marks the RNAs it contacts, to identify the direct mRNA targets of PATL2, PUM1 and PUM2 in mouse oocytes and early embryos, and test how loss of one protein shifts the others' targets.

The school

Harvard University: 42 labs on PI Pages, $1.5B a year on research, 712 research doctorates a year.

More about Harvard University

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