About

Professor Yann Chemla received his Ph.D. in physics from the University of California, Berkeley in 2001. Trained as a condensed matter experimentalist, he developed an interest in biophysics through his study of magnetotactic bacteria and his development of a magnetic nanoparticle-based biosensor. He completed his transition to biophysics as a postdoctoral fellow in Professor Carlos Bustamante's laboratory at Berkeley, where he trained in single-molecule methods, using optical tweezers to study DNA packaging in viruses. Since joining the Department of Physics at the University of Illinois, Urbana-Champaign in 2007, he has focused on understanding the mechanisms of molecular machines within living cells, employing powerful biophysical techniques to observe these processes at the single-molecule level. His research involves developing new methodologies, such as high-resolution optical tweezers and combined optical trap-fluorescence microscopy, to investigate conformational dynamics, cargo transport, and subcellular protein condensates. Professor Chemla's work aims to elucidate how these molecular machines operate, interact, and are regulated, contributing significantly to the fields of biological physics and biophysics.

Research topics

• Biology
• Computer Science
• Physics
• Genetics
• Molecular biology
• Biophysics
• Nanotechnology
• Mechanical engineering
• Engineering
• Biochemistry
• Cell biology
• Pathology
• Immunology
• Chemistry
• Materials science
• Optics
• Biological system

Selected publications

• Base-pair scale dynamics of a repair helicase on DNA lesions reveal varied damage-sensing mechanisms

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-03

  articleOpen accessSenior authorCorresponding

  Nucleotide excision repair (NER) is a cellular pathway that removes DNA lesions caused by ultraviolet light and various mutagens. A critical component of the NER machinery is XPD helicase, which unwinds the duplex around the damage, allowing its excision and repair. XPD has also been increasingly implicated in sensing and verifying DNA damage. However, the detailed mechanisms by which XPD responds to DNA damage have to-date remained unclear. Here, we use optical tweezers to perform real-time, high-precision measurements of single molecules of XPD as they encounter a variety of well-defined DNA modifications, including a cyclobutane pyrimidine dimer (CPD), a natural substrate for NER. The observed XPD dynamics reveal different behaviors depending on the damage type and the relative orientations of the DNA fork, damage, and helicase. Most notably, XPD displays an almost complete inability to unwind past a CPD on the translocated strand, and instead exhibits a short pause around the lesion-though not a stall-followed by retreat. Combining the base pair-scale XPD kinetics with structural analyses, we identify two regions of XPD sensitive to DNA modifications.

  PublisherDOI

• Larval zebrafish swim bouts in three dimensions reveal both new and redundant behaviours

  Journal of The Royal Society Interface · 2025-08-01 · 1 citations

  article

  Two-dimensional swimming of larval zebrafish has been studied extensively. We use a three-dimensional imaging system and neural network for pose estimation to study their three-dimensional behaviour. We answer two questions: (i) are spontaneous or delayed-onset turns from free swim, dark flash and acoustic startle experiments objectively differentiable? and (ii) could larvae use stochastic selection among responses, 'feinting' during an escape? Our analysis identifies two new major modes of dorso-ventral displacement. The first half-cycle of swim bouts contains most of the information to distinguish behaviours. Dimensionality reduction as previously applied to nematodes and fruit flies reveals four clusters of swimming behaviour: the previously classified short-latency C-turns (SLCs), O-turns, free swims and a behaviour we term 'voluntary turn', which comprises turns during free swimming and time-delayed turns during dark flash and acoustic startle experiments that cannot be distinguished even when additional half-cycles are included in the analysis. Unlike previous clustering analyses, we provide a physical picture of behavioural clusters in terms of two coordinates. The larvae also engage in a new behaviour: the vertical component of the SLC enables the animal to either extend the initial direction or switch it in the middle. We rationalize this behaviour as a feinting response for predator evasion.

  PublisherDOI

• Measurement of bacteriophage infection kinetics in optically trapped, motile E. coli cells

  2024-10-02

  articleSenior author

  We use a combination of optical trapping, microfluidics, and fluorescence microscopy to track individual, motile E. coli cells during infection by fluorescently labeled bacteriophages. Dual-trap optical tweezers immobilize swimming cells in a flow chamber, into which phages can be perfused. We measure the absorption of phages onto the cell surface with fluorescence imaging, while simultaneously monitoring the cell’s flagellar rotation with the optical traps. Utilizing the flagellar rotation frequency as a proxy for proton motive force, we examine phage-induced changes to E. coli’s membrane potential. These measurements reveal perturbations to host membrane integrity by phage attachment, followed by its recovery. This technique allows us to illuminate for the kinetics of viral infection of cells at the level of individual phages and bacteria.

  PublisherDOI

• Coinfecting phages impede each other’s entry into the cell

  Current Biology · 2024-06-14 · 22 citations

  articleOpen access
  PublisherOA PDFDOI

• Temperature-jump microscopy and interaction of Hsp70 heat shock protein with a client protein in vivo

  Methods · 2024-10-01 · 1 citations

  articleOpen access

  • Temperature jump microscopy of live zebrafish larvae can study stress response. • Clean imaging is obtained by expressing fluorescent proteins in just a few cells. • Automated feedback and focusing mitigates temperature drift during experiments. • Hsp70 binds a client protein in vivo , while an inactive mutant does not. Biomolecular processes such as protein–protein interactions can depend strongly on cell type and even vary within a single cell type. Here we develop a microscope with a Peltier-controlled temperature stage, a laser temperature jump to induce heat stress, and an autofocusing feature to mitigate temperature drift during experiments, to study a protein–protein interaction in a selected cell type within a live organism, the zebrafish larva. As an application of the instrument, we show that there is considerable cell-to-cell variation of the heat shock protein Hsp70 binding to one of its clients, phosphoglycerate kinase in vivo . We adapt a key feature from our previous folding study, rare transformation of cells within the larva, so that individual cells can be imaged and differentiated for cell-to-cell response. Our approach can be extended to other organisms and cell types than the ones demonstrated in this work.

  PublisherDOI

• Co-infecting phages impede each other’s entry into the cell

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-06-05 · 2 citations

  preprintOpen access

  Bacteriophage lambda tunes its propensity to lysogenize based on the number of viral genome copies inside the infected cell. Viral self-counting is believed to serve as a way of inferring the abundance of available hosts in the environment. This interpretation is premised on an accurate mapping between the extracellular phage-to-bacteria ratio and the intracellular multiplicity of infection (MOI). However, here we show this premise to be untrue. By simultaneously labeling phage capsids and genomes, we find that, while the number of phages landing on each cell reliably samples the population ratio, the number of phages entering the cell does not. Single-cell infections, followed in a microfluidic device and interpreted using a stochastic model, reveal that the probability and rate of individual phage entries decrease with MOI. This decrease reflects an MOI-dependent perturbation to host physiology caused by phage landing, evidenced by compromised membrane integrity and loss of membrane potential. The dependence of phage entry dynamics on the surrounding medium is found to result in a strong impact of environmental conditions on the infection outcome, while the protracted entry of co-infecting phages increases the cell-to-cell variability in infection outcome at a given MOI. Our findings demonstrate the previously unappreciated role played by entry dynamics in determining the outcome of bacteriophage infection.

  PublisherOA PDFDOI

• Rapid automated 3-D pose estimation of larval zebrafish using a physical model-trained neural network

  PLoS Computational Biology · 2023-10-23 · 7 citations

  articleOpen accessSenior authorCorresponding

  Quantitative ethology requires an accurate estimation of an organism's postural dynamics in three dimensions plus time. Technological progress over the last decade has made animal pose estimation in challenging scenarios possible with unprecedented detail. Here, we present (i) a fast automated method to record and track the pose of individual larval zebrafish in a 3-D environment, applicable when accurate human labeling is not possible; (ii) a rich annotated dataset of 3-D larval poses for ethologists and the general zebrafish and machine learning community; and (iii) a technique to generate realistic, annotated larval images in different behavioral contexts. Using a three-camera system calibrated with refraction correction, we record diverse larval swims under free swimming conditions and in response to acoustic and optical stimuli. We then employ a convolutional neural network to estimate 3-D larval poses from video images. The network is trained against a set of synthetic larval images rendered using a 3-D physical model of larvae. This 3-D model samples from a distribution of realistic larval poses that we estimate a priori using a template-based pose estimation of a small number of swim bouts. Our network model, trained without any human annotation, performs larval pose estimation three orders of magnitude faster and with accuracy comparable to the template-based approach, capturing detailed kinematics of 3-D larval swims. It also applies accurately to other datasets collected under different imaging conditions and containing behavioral contexts not included in our training.

  PublisherOA PDFDOI

• Optical traps induce fluorophore photobleaching by two-photon excitation

  Biophysical Journal · 2023-10-11 · 1 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Flagellar dynamics reveal fluctuations and kinetic limit in the Escherichia coli chemotaxis network

  Scientific Reports · 2023-12-21 · 4 citations

  articleOpen accessSenior author

  The Escherichia coli chemotaxis network, by which bacteria modulate their random run/tumble swimming pattern to navigate their environment, must cope with unavoidable number fluctuations ("noise") in its molecular constituents like other signaling networks. The probability of clockwise (CW) flagellar rotation, or CW bias, is a measure of the chemotaxis network's output, and its temporal fluctuations provide a proxy for network noise. Here we quantify fluctuations in the chemotaxis signaling network from the switching statistics of flagella, observed using time-resolved fluorescence microscopy of individual optically trapped E. coli cells. This approach allows noise to be quantified across the dynamic range of the network. Large CW bias fluctuations are revealed at steady state, which may play a critical role in driving flagellar switching and cell tumbling. When the network is stimulated chemically to higher activity, fluctuations dramatically decrease. A stochastic theoretical model, inspired by work on gene expression noise, points to CheY activation occurring in bursts, driving CW bias fluctuations. This model also shows that an intrinsic kinetic ceiling on network activity places an upper limit on activated CheY and CW bias, which when encountered suppresses network fluctuations. This limit may also prevent cells from tumbling unproductively in steep gradients.

  PublisherOA PDFDOI

• Helicase Activity Modulation with On-Demand Light-Based Conformational Control

  Journal of the American Chemical Society · 2023-09-22 · 5 citations

  articleOpen accessCorresponding

  Engineering a protein variant with a desired role relies on deep knowledge of the relationship between a protein's native structure and function. Using our structural understanding of a regulatory subdomain found in a family of DNA helicases, we engineered novel helicases for which the subdomain orientation is designed to switch between unwinding-inactive and -active conformations upon trans–cis isomerization of an azobenzene-based crosslinker. This on-demand light-based conformational control directly alters helicase activity as demonstrated by both bulk phase experiments and single-molecule optical tweezers analysis of one of the engineered helicases. The “opto-helicase” may be useful in future applications that require spatiotemporal control of DNA hybridization states.

  PublisherDOI

Recent grants

• Mechanisms of regulation of DNA repair helicases

  NIH · $1.4M · 2016–2021

• CAREER: Investigation of DNA-binding Protein Dynamics With High-resolution Optical Traps

  NSF · $810k · 2010–2016

• NIH Grant R21RR025341

  NIH · $535k · 2012

• PFC: Center for the Physics of Living Cells

  NSF · $10.8M · 2014–2023

• Linking Kinetics, Subunit Coordination & Structure of a Viral DNA Packaging Motor

  NIH · $1.5M · 2016–2023

Frequent coauthors

• Carlos Bustamante

  University of California, Berkeley

  42 shared

• Taekjip Ha

  Howard Hughes Medical Institute

  42 shared

• Jeffrey R. Moffitt

  Boston VA Research Institute

  25 shared

• H. L. Grossman

  25 shared

• John Clarke

  23 shared

• Ido Golding

  22 shared

• Martin Gruebele

  18 shared

• Mark Alper

  Howard Hughes Medical Institute

  15 shared

Education

• Ph.D., Physics

  University of California Berkeley

  2001

Awards & honors

• NSF CAREER award
• Sloan Foundation Research Fellowship
• Fellow of the American Physical Society