PhD POSITION: Physics-Informed Digital Holography and Optical Tweezers for Early Bacterial Biofilm Nucleation (M/F)

Job Description

Thesis Subject

Physics-Informed Digital Holography and Optical Tweezers for Early Bacterial Biofilm Nucleation

Your Work Environment

Bacterial biofilms are structured communities of bacteria embedded in a self-produced extracellular matrix. They are the dominant bacterial lifestyle in many natural and clinical environments, and they are of broad practical importance because they can strongly enhance bacterial tolerance to antibiotics, immune responses, and hydrodynamic stress. Yet the physical mechanisms governing the earliest steps of biofilm nucleation remain poorly understood.
In the traditional picture, biofilm formation begins when a freely swimming bacterium encounters a liquid-solid interface, adheres, and subsequently undergoes physiological changes that promote matrix production and sessile growth. However, this initial transition from freely swimming to surface-attached life is difficult to capture experimentally because it is rare, rapid, and highly heterogeneous from cell to cell. More generally, it remains unclear whether irreversible attachment is purely stochastic, or whether some cells are already mechanically or physiologically predisposed to nucleate a biofilm. In addition, growing evidence suggests that nucleation may also occur through the formation of small aggregates in suspension, before any permanent interaction with an interface.
Addressing these questions requires approaches that combine quantitative physics, advanced microscopy, and controlled perturbation at the single-cell level. Digital holographic microscopy enables label-free three-dimensional tracking of bacteria and small aggregates in relatively large sample volumes, making it well suited to rare nucleation events and the dynamics that precede them. Optical tweezers, by contrast, enable direct mechanical perturbation of individual cells and controlled interrogation of cell-interface or cell-cell interactions. Together, these methods provide a powerful framework for studying early biofilm nucleation as a problem in single-cell biophysics and non-equilibrium soft matter.
The student will receive interdisciplinary training at the interface of optics, biophysics, microbiology, and statistical physics. They will gain hands-on experience in digital holographic microscopy, optical tweezers, microscope development, quantitative image analysis, forward modeling of optical signals, inverse problems, Python and Matlab programming, and, depending on the direction of the project, microfluidics and bacterial culture.
The PhD student will work within the Physics and Mechanics of Biological Systems team at the Centre de Biologie Structurale in Montpellier, in a highly interdisciplinary environment combining physics, biology, and advanced instrumentation. The team is highly interactive and dynamic, and the student will interact closely with experimentalists and theorists in the group as well as with external collaborators in microscopy, soft matter, and bacterial physiology. The Centre de Biologie Structurale is an interdisciplinary and international research institute located in Montpellier, with expertise spanning optical microscopy, optical and magnetic tweezers, atomic force microscopy, NMR, X-ray crystallography, bioinformatics, bioengineering, and biomolecular modeling.

Constraints and risks

We seek a highly motivated candidate with a background in physics and a strong interest in optics, soft matter, statistical mechanics, or quantitative biophysics. Strong programming skills are essential, ideally in Python and/or Matlab.
• training in physics, optics, biophysics, soft matter, statistical mechanics, or a related discipline;
• strong taste for theory, quantitative modeling, and data analysis;
• genuine motivation to carry out demanding hands-on experiments;
• interest in digital holographic microscopy, optical tweezers, optical modeling, light scattering, inverse problems, or advanced microscopy;
• ability to move between modeling, image analysis, instrumentation, and biological experiments;
• curiosity, rigor, independence, and creativity in troubleshooting experimental and computational problems;
• enthusiasm for working in an interdisciplinary environment at the interface of physics, biology, and instrumentation.
Experience with optical tweezers, optical modeling, microscopy, bacterial systems, or microfluidics would be particularly valuable, but is not required. High-level English communication skills are an asset; no knowledge of French is required.
Activités:
• develop physics-based forward models for optical signals measured in digital holographic microscopy and optical tweezers;
• build fitting and inference tools to extract three-dimensional position, orientation, distance to an interface, and signatures of wobble or aggregate structure from experimental data;
• use digital holographic microscopy to image bacteria and small aggregates in three dimensions near interfaces and in bulk suspension;
• track single bacteria near surfaces and quantify pre-attachment features such as speed, orientation, near-wall residence time, approach angle, reversals, and rotational dynamics;
• perform optical tweezer experiments to bring individual bacteria into controlled contact with interfaces and, later, to probe cell-cell interactions;
• analyze how contact duration, optical force, and repeated collisions influence adhesion probability;
• carry out quantitative image analysis, time series analysis, inverse modeling, and statistical analysis;
• program primarily in Python, and possibly Matlab;
• participate in bacterial culture, sample preparation, and, depending on the direction of the project, microfluidics or related wet-lab activities;
• present results in group meetings, scientific workshops, conferences, and publications.

The project aims to uncover the physical states and interactions that precede bacterial biofilm nucleation by combining quantitative experiments and physics-based modeling in two complementary optical platforms: digital holographic microscopy and optical tweezers. The central question is whether bacteria that initiate biofilms, either by irreversible attachment at a liquid-solid interface or by early aggregation in bulk, display distinctive optical, dynamical, or mechanical signatures before nucleation occurs.
The PhD will be structured in two stages. The core of the thesis will focus on surface nucleation at a liquid-solid interface, from holographic imaging of freely swimming bacteria near surfaces to controlled attachment experiments using optical tweezers. Depending on progress, the project will then extend to early aggregation in bulk suspension, using the same combination of holographic imaging, optical modeling, and controlled mechanical perturbation.
Applications will be reviewed on a rolling basis until the position is filled. Candidates should provide a CV, and a short cover letter describing research interests dans fit with the proposed position.

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

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