About

Thomas Gregor is a Professor of Physics at Princeton University and a member of the Lewis-Sigler Institute for Integrative Genomics. His research focuses on providing quantitative descriptions of the complex biological systems to understand how these systems derive from general physical principles. Working at the interface between physics and biology, Gregor combines theory and experiment to explore the fundamental distinctions between inanimate and living systems, operating under the belief that the same physical laws govern both. His group pursues a physics-style approach that integrates state-of-the-art experimental techniques, often developing new measurement methods in living systems, with sophisticated data analysis to rigorously test simple models and theories. Gregor's work aims to uncover new areas of physics emerging from the study of life, particularly how precise patterns of multicellular organization arise from spatially complex and rapidly evolving molecular events, and how fluctuations and long-range DNA interactions impose physical limits on information flow and reliable cellular decision-making. Gregor's academic background includes a Master in Physics from Geneva University (1999), a Master in Chemistry from Princeton University (2001), and a Ph.D. in Biophysics from Princeton University (2005). He was a JSPS Fellow at Tokyo University from 2006 to 2009 before joining Princeton as an Assistant Professor of Physics in 2009, becoming Associate Professor in 2015 and full Professor in 2019.

Research topics

• Biology
• Genetics
• Cell biology
• Artificial Intelligence
• Computational biology
• Computer Science
• Evolutionary biology
• Neuroscience
• Cognitive science
• Epistemology
• Ecology

Selected publications

• Characeen Österreichs. Checkliste, Atlas und Rote Liste der Armleuchteralgen (Charophyceae)*

  2025-07-22

  reportOpen accessSenior author

  In the course of the project “Charophytes of Austria”, 7.577 records of stoneworts have been documented from 2005 to 2025. With the collected data and considering also historical records, we compiled a monograph of this group for the first time for Austria, including a checklist, species distribution maps and a Red List. A total of 35 species has been identified. Species records and IUCN Red List categories to classify their endangerment are provided for each federal state of Austria and habitats therein. The monograph is divided in two parts. The general section deals with the history of research with special emphasis on flora aspects, systematics and nomenclature, ecology and physiology, and nature conservation. The special section describes habitats, causes of endangerment, altitudinal distribution, morphology, ecology, population development and distribution of individual species, with references and distribution maps of all species provided. The data collected in the project were compiled in the database “Characeae Austria” and are available on the internet.

  PublisherDOI

• Fine-tuning mechanical constraints uncouples patterning and gene expression in murine pseudo-embryos

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-29 · 2 citations

  preprintOpen accessSenior authorCorresponding

  Abstract The interplay between mechanical forces and genetic programs is fundamental to embryonic development, yet how these factors independently or jointly influence morphogenesis and cell fate decisions remains poorly understood. Here, we fine-tune the mechanical environment of murine gastruloids, three-dimensional in vitro models of early embryogenesis, by embedding them in bioinert hydrogels with precisely tunable stiffness and timing of application. This approach reveals that external constraints can selectively influence transcriptional profiles, patterning, or morphology, depending on the level and timing of mechanical modulation. Gastruloids embedded in ultra-soft hydrogels (< 30 Pa) elongate robustly, preserving both anteroposterior patterning and transcriptional profiles. In contrast, embedding at higher stiffness disrupts polarization while leaving gene expression largely unaffected. Conversely, earlier embedding significantly impacts transcriptional profiles independently of polarization defects, highlighting the uncoupling of patterning and transcription. These findings suggest that distinct cellular states respond differently to external constraints. Live imaging and cell tracking imply that impaired cell motility underlies polarization defects, underscoring the role of mechanical forces in shaping morphogenesis independently of transcriptional changes. By allowing precise control over external mechanical boundaries, our approach provides a powerful platform to dissect how physical and biochemical factors interact to orchestrate early embryonic development.

  PublisherOA PDFDOI

• Deriving a genetic regulatory network from an optimization principle

  Proceedings of the National Academy of Sciences · 2025-01-03 · 18 citations

  articleOpen access

  Many biological systems operate near the physical limits to their performance, suggesting that aspects of their behavior and underlying mechanisms could be derived from optimization principles. However, such principles have often been applied only in simplified models. Here, we explore a detailed mechanistic model of the gap gene network in the Drosophila embryo, optimizing its 50+ parameters to maximize the information that gene expression levels provide about nuclear positions. This optimization is conducted under realistic constraints, such as limits on the number of available molecules. Remarkably, the optimal networks we derive closely match the architecture and spatial gene expression profiles observed in the real organism. Our framework quantifies the tradeoffs involved in maximizing functional performance and allows for the exploration of alternative network configurations, addressing the question of which features are necessary and which are contingent. Our results suggest that multiple solutions to the optimization problem might exist across closely related organisms, offering insights into the evolution of gene regulatory networks.

  PublisherDOI

• FORMING A LARGE, MULTICENTRE HERBARIUM: HERBARIUM HAUSSKNECHT (JE) JOINS HERBARIUM SENCKENBERGIANUM

  Taxon · 2025-04-01

  articleOpen access

  Natural history collections constitute Senckenberg's largest and most important research infrastructure. With more than 45 million items, they represent the most extensive natural history collections in Germany, being among the top 10 respective collections worldwide. The Senckenberg herbarium collections (Herbarium Senckenbergianum | Senckenberg - Leibniz Institution for Biodiversity and Earth System Research) are decentralized at the locations Frankfurt (FR), Görlitz (GLM), Weimar (IQW) and Wilhelmshaven, the latter being part of FR (Fig. 1). Herbaria FR and GLM were founded in 1817 and 1811, respectively, while the botanical collections at Weimar and Wilhelmshaven were established more recently. After the integration of GLM into Herbarium Senckenbergianum in 2009, scientific collaboration was strengthened and diversified, access to the collections improved and technical and administrative procedures standardized, while maintaining the physical integrity and regional role of the herbaria. Additionally, the IQW herbarium in Weimar and a center for dinophyte taxonomy in Wilhelmshaven were established (Otte & al., 2011). Recently, an unprecedented step in the landscape of German herbaria was taken with the foundation of the Senckenberg Institute for Plant Form and Function (SIP) in cooperation with Friedrich Schiller University Jena (SIP, Senckenberg Institute for Plant Form and Function). The core of this new research facility is Herbarium Haussknecht (JE), which was established by Carl Haussknecht as a private foundation in 1896. It hosts over 3.6 million specimens and is thus ranked among the 20 largest herbaria worldwide (Thiers, 2022). Herbarium Haussknecht became a member of Herbarium Senckenbergianum in April 2024. With currently more than 5.6 million specimens (Table 1), the expanded Herbarium Senckenbergianum is now responsible for ca. 25% of all herbarium (and fungarium) specimens preserved in Germany (Borsch & al., 2020). Over the last decade, collections of Herbarium Senckenbergianum jointly experienced a mean annual increase of ca. 72.000 specimens, implying ca. 6.5 million specimens will likely be preserved by 2035 (Fig. 2). Following Senckenberg's philosophy and institutional structure, the spatial allocation of the collections and their codes are retained, so that neither the successful tradition nor the important regional ties (e.g., to the Thuringian Botanical Society) and responsibilities are interrupted. A key goal of Senckenberg is to improve access to specimens for both science and society through digitization, and to unlock the treasure trove of data stored in its herbaria. The last decade witnessed a revolution in new techniques being applied to natural history collections in general, and herbaria in particular. This includes imaging (e.g., Schneider & al., 2017; Younis & al., 2020), spectroscopic techniques (e.g., Kothari & al., 2023; Kühn & al., 2024, 2025) and, increasingly, genomic approaches (e.g., Burbano & Gutaker, 2023). Data science and artificial intelligence dramatically improve data extraction and analysis and will impact taxonomy and species discovery (e.g., Hussein & al., 2022; Irschick & al., 2022; Shirai & al., 2022; Wilde & al., 2023; Jones & al., 2024; Karbstein & al., 2024). The concept of the (digital) “extended specimen” embraces these developments (Webster, 2017; Lendemer & al., 2020; Miralles & al., 2020; Hardisty & al., 2022) and has led to extensive international initiatives (e.g., www.dissco.eu, Koureas & al., 2023). These aim to establish closely interlinked physical as well as virtual research platforms providing an infrastructure for a broad range of questions (Johnson & al., 2023). The main idea behind the integration of JE in Herbarium Senckenbergianum is thus to foster collection-based research, curation, and development towards the idea of a global metaherbarium as an open-access resource (Davis & al., 2023). JE benefits from the unique experience Senckenberg has gained over 15 years of integrating natural history collections at 11 locations in Germany in a federal structure (Fig. 1). Along these lines, Senckenberg has coined the term “collectomics” to address the vastly enlarged range of research, made possible by combining the broad variety of new methods with digital integration, modern data science and knowledge derived from specimens. This expands on the concept of museomics, which was originally defined to focus on molecular data generated from museum specimens. As such, collectomics encompasses metadata, images, traits, DNA, and other data that will be extracted in the future with yet unknown applications, all of which being connected to environmental data and other historical contextual information (Collectomics Consortium, in press). This allows us to retrieve biodiversity information from population to ecosystem level, especially with regard to climate and land use change as well nature conservation and biological invasions. To meet these challenges, the team of Herbarium Senckenbergianum comprises 28 scientists covering all taxonomic groups. The focus of individual research teams ranges from systematics, biodiversity genomics, plant ecology, conservation to plant functional ecology. Most recently, a professorship for IT approaches in collection-based research has been established in Jena. Our scientific staff is supported by 19 technical employees and ca. 40 volunteers. The latter personnel does not only support daily handling of specimens and databasing but also contribute to the overall taxonomic expertise and breadth. The immediate effect for scientists is similar to that following the merge of GLM with Herbarium Senckenbergianum in 2009 (Otte & al., 2011): any scholar interested in specimens from the joint Herbarium Senckenbergianum can contact one of the participating institutions, either to visit our collections or to request specimen loans, and receive material from all herbaria in one place or through a single loan. This also includes the service for DNA extractions from specimens, which is organized centrally by the Grunelius Möllgard Laboratory (DNA-Bank | Senckenberg Society for Nature Research) at FR in close coordination with the responsible herbarium curators at each of the different locations. Another main goal is the harmonization of collection strategies in order to better document botanical diversity at different levels. On a national scale, Herbarium Senckenbergianum now covers a German longitudinal transect from western Germany, in particular Hesse (FR), via central Germany, especially Thuringia (JE), to eastern Germany, especially Saxony (GLM) (Fig. 1). At the national level, our collections already form the basis for the provision of identification aids (Müller & al., 2021), virtual herbaria of validated specimens (https://virtherbard.senckenberg.de; https://bestikri.senckenberg.de) and databases (https://chromosomes.senckenberg.de) including local floras (www.flora-frankfurt.de). Access to most of these databases is now centralized on the national information portal “Floraweb” (https://www.floraweb.de/), which is hosted by the German federal government. At the international scale, the biogeographical focus of FR is on vascular plants of Africa (http://www.africanplants.senckenberg.de/root/index.php) and – increasingly so – on Central America, from where 200,000+ specimens will be incorporated into FR soon. GLM's core area is northern and inner Eurasia, while JE houses huge numbers of specimens from Cuba as well as the Middle East. Apart from vascular plants, Herbarium Senckenbergianum also employs experts for algae (FR, Wilhelmshaven), phytoparasitic fungi (GLM), lichens (FR, GLM), and has established a new professorship for bryophytes (JE). The recently launched initiative “CryptoHub” will improve the visibility of Senckenberg's bryophyte and lichen collections. All Senckenberg herbaria have considerable coverage of global liverwort diversity and a particularly large collection of type material. For the lichens, Herbarium Senckenbergianum is among the top 10 reference collections for Lecanoromycetes worldwide (according to GBIF), which will be further complemented by the JE collection. IQW remains Senckenberg's Quaternary fossil facility, and Wilhelmshaven represents the Centre of Excellence for Dinophyte Taxonomy (CEDiT, https://www.dinophyta.org/). The founding of the Senckenberg Institute for Plant Form and Function (SIP) at Jena and the extension of Herbarium Senckenbergianum were implemented in the course of the “Anthropocene Biodiversity Loss” program, which is now permanently established at Senckenberg and was made possible thanks to substantial permanent funding by the Leibniz Association. We also thank the technicians and supporters of Herbarium Senckenbergianum: Luisa Otto, Heike Kappes, Viola Ziller, Micheline Middeke, Gerald Utschig, Evelin Haase, Susann Döring, Maurice Scheidler, Renate Christian, Michaela Schwager, Rainer Döring, Jörg Lorenz, Noel Lichtner, Siegfried Bräutigam, Petra Gebauer, Hans-Werner Otto, Herbert Boyle, Andrea Todt, Gabriele Reislöhner, Sergey Pfaff, Hans-Joachim Zündorf, Anne-Kathrin Pilz and the large number of further volunteers that cannot all be mentioned here.

  PublisherOA PDFDOI

• Transcription factor clusters as information transfer agents

  Science Advances · 2025-01-01 · 13 citations

  articleOpen accessSenior authorCorresponding

  Deciphering how genes interpret information from transcription factor (TF) concentrations within the cell nucleus remains a fundamental question in gene regulation. Recent advancements have revealed the heterogeneous distribution of TF molecules, posing challenges to precisely decoding concentration signals. Using high-resolution single-cell imaging of the fluorescently tagged TF Bicoid in living Drosophila embryos, we show that Bicoid accumulation in submicrometer clusters preserves the spatial information of the maternal Bicoid gradient. These clusters provide precise spatial cues through intensity, size, and frequency. We further discover that Bicoid target genes colocalize with these clusters in an enhancer-binding affinity-dependent manner. Our modeling suggests that clustering offers a faster sensing mechanism for global nuclear concentrations than freely diffusing TF molecules detected by simple enhancers.

  PublisherDOI

• An integrated quantitative single-objective light-sheet microscope for subcellular dynamics in embryos and cultured multicellular systems

  HAL (Le Centre pour la Communication Scientifique Directe) · 2025-12-29

  preprintOpen accessSenior author

  Quantitative imaging of subcellular processes in living embryos, stem-cell systems, and organoid models requires microscopy platforms that combine high spatial resolution, fast volumetric acquisition, long-term stability, and minimal phototoxicity. Single-objective light-sheet approaches based on oblique plane microscopy (OPM) are well suited for live imaging in standard sample geometries, but most existing implementations lack the optical calibration, timing precision, and end-to-end integration required for reproducible quantitative measurements. Here we present a fully integrated and quantitatively characterized OPM platform engineered for dynamic studies of transcription and nuclear organization in embryos, embryonic stem cells, and three-dimensional culture systems. The system combines high numerical aperture remote refocusing with tilt-invariant light-sheet scanning and hardware-timed synchronization of laser excitation, galvo scanning, and camera readout. We provide a comprehensive characterization of the optical performance, including point spread function, sampling geometry, usable field of view, and system stability, establishing a well-defined framework for quantitative volumetric imaging. To support high-throughput operation, we developed a unified acquisition and reconstruction pipeline that enables real time volumetric imaging at hardware-limited rates while preserving deterministic timing and reproducible geometry. Using this platform, we demonstrate quantitative three-dimensional imaging of MS2-labeled transcription sites in living Drosophila embryos, cultured mouse embryonic stem cells, and mESC-derived gastruloids, enabling extraction of transcriptional intensity traces across diverse biological contexts. This work establishes OPM as a robust and quantitatively calibrated single-objective light-sheet platform for transcription imaging in complex living systems.

  PublisherDOI

• The Physics of Sustainability: Material and Power Constraints for the Long Term

  ArXiv.org · 2025-12-11 · 1 citations

  preprintOpen accessSenior author

  Much of today's sustainability discourse emphasizes efficiency, clean technologies, and smart systems, but largely underestimates fundamental physical constraints relating to energy-matter interactions. These constraints stem from the fact that Earth is a materially closed yet energetically open system, driven by the sustained but low power-density flux of solar radiation. This Perspective reframes sustainability within these axiomatic limits, integrating relevant timescales and orders of magnitude. We argue that fossil-fueled industrial metabolism is inherently incompatible with long-term viability, while post-fossil systems are surface-, materials-, and power-intensive. Long-term sustainability must therefore be defined not only by how much energy or material is used, but also by how it is used: favoring organic, carbon-based chemistry with limited reliance on purified metals, operating at low power density, and maintaining low throughput rates. Achieving this requires radical technological shifts toward life-compatible systems and biogeochemical circular processes, and, likely as a consequence, a paradigm change toward degrowth to a steady-state. These two shifts are mutually reinforcing and together provide the necessary foundation for any viable future.

  PublisherOA PDFDOI

• Invariant non-equilibrium dynamics of transcriptional regulation optimize information flow.

  PubMed · 2025-07-16

  preprintOpen access

  Eukaryotic gene regulation is based on stochastic yet controlled promoter switching, during which genes transition between transcriptionally active and inactive states. Despite the molecular complexity of this process, recent studies reveal a surprising invariance of the "switching correlation time" ($T_C$), which characterizes promoter activity fluctuations, across gene expression levels in diverse genes and organisms. A biophysically plausible explanation for this invariance remains missing. Here, we show that this invariance imposes stringent constraints on minimal yet plausible models of transcriptional regulation, requiring at least four system states and non-equilibrium dynamics that break detailed balance. Using Bayesian inference on Drosophila gap gene expression data, we demonstrate that such models (i) accurately reproduce the observed $T_C$-invariance; (ii) remain robust to parameter perturbations; and (iii) maximize information transmission from transcription factor concentration to gene expression. These findings suggest that eukaryotic gene regulation has evolved to balance precision with reaction rate and energy dissipation constraints, favoring non-equilibrium architectures for optimal information transmission.

  PublisherOA PDF

• A conserved coupling of transcriptional ON and OFF periods underlies bursting dynamics

  Nature Structural & Molecular Biology · 2025-07-15 · 5 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Size-dependent temporal decoupling of morphogenesis and transcriptional programs in pseudoembryos

  Science Advances · 2025-08-22 · 8 citations

  articleOpen accessSenior authorCorresponding

  Understanding the interplay between cell fate specification and morphogenetic changes remains a challenge in developmental biology. Gastruloids, stem cell models of postimplantation mammalian development, provide a platform to address this question. Here, using quantitative live imaging and transcriptomic profiling, we show that physical parameters, particularly system size, affect morphogenetic timing and outcomes. Larger gastruloids exhibit delayed symmetry breaking, increased multipolarity, and prolonged axial elongation, with morphogenesis driven by size. Despite these variations, transcriptional programs and cell fate composition remain stable across a broad size range, illustrating the scaling of gene expression domains. In particular, extreme sizes show distinct transcriptional modules and shifts in gene expression patterns. Size perturbation experiments rescued the morphogenetic and pattern phenotypes observed in extreme sizes, demonstrating the adaptability of gastruloids to their effective system size. These findings position gastruloids as versatile models for dissecting spatiotemporal coordination in mammalian development and reveal how physical constraints can decouple gene expression programs from morphogenetic progression.

  PublisherOA PDFDOI

Recent grants

• Control of the 4D chromatin landscape underlying gene activity during development

  NIH · $3.2M · 2020–2025

• The Biophysical and Molecular Mechanisms of Reliability in Development

  NIH · $4.9M · 2011–2026

• Controlling collective behavior in eukaryotic cell populations

  NIH · $1.1M · 2012–2018

• NIH Grant U01EB021239

  NIH · $1.1M · 2020

• NIH Grant U01DA047730

  NIH · $740k · 2020

Frequent coauthors

• Benjamin Zoller

  Centre National de la Recherche Scientifique

  84 shared

• Eric Wieschaus

  Princeton University

  74 shared

• William Bialek

  Princeton University

  72 shared

• Ralf Hand

  45 shared

• Mariela D. Petkova

  Harvard University

  38 shared

• Lev Barinov

  Princeton University

  22 shared

• Gašper Tkačik

  Institute of Science and Technology Austria

  21 shared

• Gentian Muhaxheri

  City University of New York

  20 shared

Labs

• Laboratory for the Physics of LifePI

  The Laboratory for the Physics of Life is a biophysics research laboratory of Thomas Gregor at the Physics Department of Princeton University. The main focus of the lab is at the interface of physics and biology, and it pursues quantitative approaches to systems and developmental biology.