PIPages
Labs

Warren Zipfel

Cornell University, NY·Biomedical Engineering

A cell's DNA is not stored as a loose tangle — it is folded in three dimensions, and which stretches of DNA sit near each other helps decide which genes turn on. That folding changes as cells differentiate, respond to stress, or begin to become diseased.

Fields

Biomedical Engineering

Biophysics

Genetics

Topics

Femto-seq

two-photon excitation

confocal microscopy

Grants
1 known grant, through Jan 2027

What they work on

  1. Design and build an automated dual confocal/two-photon microscope that can image a cell population, locate fluorescently labeled nuclear regions of interest, and irradiate them with femtosecond pulses at high throughput.
  2. Develop a chromatin isolation pipeline using new microfluidic designs to efficiently purify biotin-tagged DNA from isolated nuclei and prepare it for sequencing.
  3. Demonstrate Femto-seq performance quantitatively by photo-biotinylating targeted femtoliter nuclear volumes with a psoralen-biotin cross-linker, then pulling down and sequencing the locus- or region-enriched DNA.
  4. Apply Femto-seq to ask how environmental signals relayed from the cytosol into the nucleus alter genomic contacts near specific gene loci and nuclear bodies in user-selected cells.

More about the research

Existing tools capture this only partly: chromosome conformation capture (3C) methods average over millions of cells, while DNA fluorescent in situ hybridization (DNA-FISH) looks at single cells but at low throughput. This project develops a method that fills the gap, letting researchers pull out and sequence the DNA that happens to be sitting in one tiny, microscopically chosen spot inside a chosen cell's nucleus.

Why it matters

A method that links what can be seen under a microscope to actual DNA sequence could sharpen how researchers detect and characterize genetic susceptibility to disease and responses to environmental exposures, and inform treatment strategies built on that knowledge. More broadly, it offers a route to understanding how the nucleus physically rearranges itself when a cell's environment changes.

Known grants

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

Femto-seq: Targeted photo-biotinylation, pulldown and sequencing of locus and region-specific DNA from femtoliter volumes within individual cells

NIH · Feb 2023 – Jan 2027

Closest labs

David Shechner

University of Washington, WA·Biochemistry

Generate a high-confidence catalog of the proteins, transcripts and genomic loci that make up Cajal bodies, using O-MAP, an RNA-targeted proximity-biotinylation method that tags molecules near a chosen RNA inside intact cells.

Chris Xu

Cornell University, NY·Biomedical Engineering

Raise the three-photon fluorescence signal by about 10,000-fold through new lasers and imaging techniques, to image mouse brain activity with sub-cellular resolution at about 2 mm depth.

Donna Neumann

University of Wisconsin-Madison, WI·Microbiology & Immunology

Define how chromatin insulators in the HSV-1 genome form loops that silence viral genes during latency, using human neurons and Chromosome Conformation Capture circular sequencing (4C-seq).

The school

Cornell University: 37 labs on PI Pages, $1.6B a year on research, 537 research doctorates a year.

More about Cornell University

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