Decoding the molecular dance: Victoria Birkedal and Asger Hobolth receive VILLUM Synergy Grant
Associate Professor Victoria Birkedal (Department of Chemistry & iNANO) and Professor Asger Hobolth (Department of Mathematics), both from Aarhus University have received a VILLUM Synergy grant. The project unites mathematicians and biophysical chemists to turn noisy single-molecule videos into clear maps of biomolecular dynamics.
Watching molecules “dance” — and making sense of the steps
Inside living systems, biomolecules move, bind, fold and change shape. With single-molecule microscopy, researchers can follow these motions in real time—one molecule at a time. This project combines mathematical modelling with experimental biophysics to translate those signals into reliable insight about life’s molecular processes.
About the project: From mathematics to molecules
Birkedal and Hobolth co-lead the VILLUM Synergy project “Bridging hidden Markov modelling and real-time single molecule imaging.” The collaboration brings together advanced statistical modelling and single-molecule experiments to extract information about the dynamics of biomolecules from single molecule microscopy videos, that has until now remained inaccessible due to signal complexity.
Professor Hobolth contributes expertise in hidden Markov modelling (HMM), a mathematical method he previously used to study DNA evolution in population genetics and phylogenetics. In this new context, HMMs will help decode the dynamic behaviour of biomolecules observed under the microscope.
“This project is particularly exciting from a mathematical point of view because the analysis of the single molecule microscopy time series requires an extension of the traditional analyses of hidden Markov models.”
- Professor Asger Hobolth
Associate Professor Birkedal brings deep experience in single-molecule biophysics, focusing on the folding dynamics of nucleic acids and their interactions with proteins. Her group provides the experimental platform to generate high-resolution real-time imaging data and test the models in biologically relevant systems.
“Biomolecules interact and function in a complex ‘dance’. Single-molecule microscopy enables direct observation of individual biomolecules in real time. By co-developing analysis frameworks grounded in hidden Markov modelling and validating them experimentally, we aim to bring new tools for extracting deeper molecular insights.”
- Associate Professor Victoria Birkedal
What’s the scientific challenge?
While single-molecule techniques offer unprecedented resolution, interpreting the resulting time series is anything but straightforward. The data are high-dimensional, often noisy, and reflect processes that shift between hidden states. Modelling these transitions requires new mathematical tools that are both flexible and biologically grounded.
Mini-explainer: Hidden Markov models, in plain language
Imagine you hear music from a room you can’t see. From the sound alone, you guess whether people are waltzing, pausing, or speeding up. An HMM does something similar: it uses observable signals to decode the most likely hidden states—and how often transitions between them occur. That’s exactly the kind of reasoning needed to interpret single-molecule video data.
About the researchers
Victoria Birkedal leads the Single-Molecule Biophysics & Chemistry group, which develops and applies single-molecule fluorescence (incl. smFRET) to study the structure, dynamics, and function of nucleic acids and biomolecular assemblies under physiologically relevant conditions. Single Molecule BioPhysics and Chemistry Group
Asger Hobolth is Professor of Mathematics at Aarhus University, with a research focus on stochastic modelling and statistical methods for biological sequence data and time series.
About VILLUM Synergy
The VILLUM Synergy programme supports interdisciplinary, data-driven research across Danish universities. Each project is led by two Principal Investigators: one from computer science, statistics or applied mathematics, and one from a domain field (outside clinical medicine). The programme aims to generate new insights through close collaboration between methods and application. VILLUM Synergy programme
Press release by the VILLUM Foundation
The grant was announced as part of the VILLUM Foundation’s 2025 Synergy programme press release, which highlights 13 interdisciplinary data-driven projects across Danish universities. Read the full announcement here.
Contact
Associate Professor Victoria Birkedal
Department of Chemistry & Interdisciplinary Nanoscience Center (iNANO)
Aarhus University
Email: vicb@inano.au.dk
Professor Asger Hobolth
Department of Mathematics
Aarhus University
Email: asger@math.au.dk