Job Dekker

@jobdekker.bsky.social

Biologist. Chromosomes | dinoflagellates | birds. Happy in academia! Umass Chan Medical School, HHMI http://www.dekkerlab.org

For Fall 25, I made a number of in class activities very much on the theme of "Here is Chat-GPT's terrible answer to material we've just covered in this intro bio class. Tell me what's wrong with it". Well, it's a year later, and new models have been released. So let's see how it fares now:

S’il y a bien un truc qui me passionne, c’est l’ADN 🧬 Cette molécule est la raison pour laquelle je suis venu en France à mes 18 ans, ça a été mon sujet d’étude pendant des années, et c’est même mon motif préféré à intégrer aux ouvrages en tricot ou en macramé !

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I was sad to learn that my postdoctoral mentor, David Botstein, died yesterday. I started with David as a postdoc in 1998, and he had a profound effect on both my life and scientific career. He was a giant in the field of genetics, making seminal contributions in both yeast and human genetics. 1/

I had the privilege to meet artist Mary Griffiths. Mary got inspired by Hi-C maps and over zooms we spoke about Hi-C maps, patterns and drawings. Mary’s Hi-C inspired art has been exhibited eg the Royal Academy. We wrote this piece about this art-science collaboration pubs.aip.org/aip/bpr/arti...

Seeing into Hi-C: How our scientific connectivity revealed the close connections in our DNA to be a work of art

Scientific data can be beautiful. An example where the data itself have a particularly striking appearance even before any scientific meaning has been ascribed

pubs.aip.org

Excited to share my PhD work from @riscalab.bsky.social on @biorxivpreprint.bsky.social CAD-C & CADwalks –repair-free, nucleosome-resolution chromosome conformation capture with engineered TEVp-activatable CAD. CADwalks: chromosome walks of ligated CAD footprints. doi.org/10.64898/202... 1/

CAD-C: An engineered nuclease enables repair-free in situ proximity ligation and nucleosome-resolution chromosome walks in human cells

Chromosome conformation capture (3C)-derived methods have become an indispensable tool in the study of gene regulation. The three-dimensional contacts they are able to assay depend strongly on the properties of the enzyme used to fragment chromatin prior to proximity-driven ligation. Micrococcal nuclease (MNase), used in Micro-C, increases resolution at the expense of low ligation efficiency and the need for extensive enzyme titration. To overcome these limitations, we engineered a highly active, TEV protease-activatable caspase-activated DNase (CAD) to enable an efficient, low-sequence-bias, and high-resolution proximity ligation assay we call CAD-C. CAD-C was successful on the first attempt for each human cell line tested and the resulting datasets capture loops, TADs, compartments, and stripes similarly to Micro-C. However, compared to Micro-C and Hi-C, CAD-C shows enhanced sensitivity for promoter-enhancer loops. Leveraging the ligation-competent DNA ends produced by CAD cleavage, we show that CAD-C is compatible with a highly streamlined, repair-free protocol and produces multi-step CADwalks, consecutive ligations between nucleosomal or sub-nucleosomal fragments. With these walks, we probe local chromatin fiber folding contacts, nucleosomal and sub-nucleosomal footprints, and long-range nuclear organization regimes in human cell lines. CAD-C is an efficient, robust chromatin structure assay that can span sub-nucleosomal to chromosomal length scales in a single experiment. ### Competing Interest Statement V.I.R. and J.S. are inventors on a related patent application covering CAD-C (PCT application filed 2024). NIH Common Fund, https://ror.org/001d55x84, 1DP2GM150021 Irma T. Hirschl Trust, https://ror.org/01yaqvf46, Career Scientist Award Rita Allen Foundation, https://ror.org/0515k5w36, Scholar Award Stavros Niarchos Foundation, https://ror.org/0210rze73, Institute for Global Infectious Disease Research at Rockefeller University Grant Robertson Technology Development Fund at Rockefeller University Boehringer Ingelheim (Germany), https://ror.org/00q32j219, PhD Fellowship to JS U.S. National Science Foundation, https://ror.org/021nxhr62, GRFP to LAW International Human Frontier Science Program Organization, https://ror.org/02ebx7v45, Postdoctoral Cross-Disciplinary Fellowship to AO Natural Sciences and Engineering Research Council of Canada, Postgraduate fellowship to HC, Postgraduate fellowship to JLY

doi.org

When gene expression goes wrong, it can cause abnormal cellular growth, cancer, & more. HHMI Investigator Michelle Wang (Cornell University) & collaborators have discovered that nucleosomes—long thought to be obstacles to gene expression—actually help the process work more smoothly. bit.ly/4q9xA6e

Unexpected allies: DNA packaging aids gene expression | Cornell Chronicle

Researchers discovered that DNA packaging structures called nucleosomes, which have been traditionally seen as roadblocks for gene expression, actually help reduce torsional stress in DNA strands and facilitate genetic information decoding.

bit.ly