Schlissel G, Meziane M, Narducci D, Hansen AS, Li P (2024) Diffusion barriers imposed by tissue topology shape morphogen gradients. PNAS 2024 Sep 3;121(36):e2400677121. PMID 39190357
This is my most complex paper to date — both technologically and intellectually — and this is the paper I am most proud of. We discovered that Hedgehog gradients form by extracellular diffusion of Hedgehog monomers, which slide along cell membranes and occasionally jump from cell-to-cell. We found that the “jump” probability is sufficient to control the Hedgehog signaling range, suggesting novel biochemical mechanisms that evolution can use to regulate morphogen gradient length scales. To build this model, we developed a novel approach to track single molecules of Hedgehog in reconstituted Hedgehog signaling gradients. This paper disproved several legacy ideas in the Hedgehog signaling field, and unified many ideas about morphogen signaling that were previously thought to be at odds. The paper represents the core work I’ve done as a postdoc.
Schlissel G, Li P (2020) Synthetic Developmental Biology: understanding through reconstitution. Annual Review of Cell and Developmental Biology 2020 36:1, 339-357. PMID 33021822
We reviewed developmental biology literature that used reconstitution as a strategy to probe developmental questions. The literature we surveyed range from classic biochemistry to modern embryoid technologies, connected by a common conceptual reliance on “understanding through reconstitution.”
Schlissel G, Rine J (2019) The nucleosome core particle remembers its position through DNA replication and RNA transcription. PNAS. 116(41):20605-611. PMID 31511420
We established that nucleosomes present at given locus prior to DNA replication re-occupied the exact same locus after DNA replication, suggesting that nucleosomes can store and transmit epigenetic memory. Additionally, this paper established that transcription did not cause nucleosomes to “slide” locally. This work required us to build a novel biotin ligase, which we used to label and track single nucleosomes with unprecedented accuracy. This paper represents my core thesis work during my time at Berkeley.
Commentary –
Henikoff S , Ahmad K. Nucleosomes remember where they were. PNAS.
Schlissel G*, Kryzanowski MK,* Caudron F, Barral Y, Rine J. 2017. Aggregation of the Whi3 protein, not loss of heterochromatin, causes sterility in old yeast cells. Science. 355(6330):1184- 87. PMID 28302853
This paper established that yeast aging did not correspond to a loss of heterochromatin, in conflict with widely-cited reports in the literature. Furthermore, this work established that protein aggregation was responsible for the canonical observation in the yeast aging field, that old yeast cells do not respond to mating pheromone.
Commentary –
Gitler AD, Jarosz DF. Old moms say, no Sir. Science.
Bothma JP, Garcia HG, Esposito E, Schlissel G, Gregor T, Levine M. 2014. Dynamic regulation of eve stripe 2 expression reveals transcriptional bursts in living Drosophila embryos. PNAS. 111(29):10598-603. PMID 24994903
This paper reported the results of my first graduate rotation, in which we discovered that transcription from the Eve stripe 2 enhancer was “bursty,” and that the Eve stripe 2 pattern is rapidly refined within the first ~25 minutes of the 14th nuclear division cycle. Additionally, this was among the first papers to use MS2/MCP tagging to measure RNA transcription rates in live embryos.
