News
New method to monitor movement in cells
Wageningen researchers and their international collaboration partners have developed novel software that accurately maps the movements of multiple particles within bacterial cells. This technology enables scientists to monitor proteins and DNA in living cells and study their function. The researchers published their study in the scientific journal Nature Methods.
The new technology, called TARDIS, opens up novel possibilities for biological research, for example in investigating the effects of antibiotics and other medication on molecular processes within cells. "Some antibiotics work by blocking specific molecular machines in the cell," says Koen Martens, first author of the publication. The software allows the simultaneous study of the behavior of multiple machines, providing quicker insights into the effectiveness of an antibiotic.
Glitchy Movie
Visualising particles in a cell using biological techniques has been possible for some time, for example by attaching them to a kind of fluorescent particle. “But with that technique you can only track one particle at a time,” says Martens. Biomolecules move rapidly, faster than cameras can capture, resulting in a glitchy film with jumping frames. If you follow a single particle, it's manageable, as you can fill in the missing movements. “However, if two or more identical looking particles glitch, it is often impossible to determine which particle on the first frame corresponds to which on the next frame.”
Probability Calculation
This is where computational power comes into play. The developed software utilises probability calculations to compute all possible paths of the particles, taking into account biological dynamics and physical forces – amongst others. It determines which particles on each frame correspond to the particles on the subsequent frames. According to the researchers, this calculation is remarkably accurate. They tested the software on well-known movement patterns such as diffusion, under more complex conditions than was previously possible. "Our programme calculated the correct movement," says Martens. The computer does not require much information, solely the coordinates of the particles at different time points, as measured with a microscope.
For the first time, global movement patterns within cells can be measured clearly. However, Johannes Hohlbein, Associate Professor of Biophysics, points out a limitation: "The new software does not allow live monitoring of an individual particle, but we can now achieve higher throughput in processing data" he explains. Think of it like an overhead view of a flock of sheep: the computer predicts how the flock moves, but doesn't track the path of each individual sheep.
DNA Repair
The idea for the software originated in 2020 during Martens' doctoral research at WUR. "His dissertation was already so lengthy that there was no room for this study," says Hohlbein. Therefore, Martens and Hohlbein further developed the idea later on, together with colleagues at Carnegie Mellon University and the University of Bonn, where Martens currently works. In his ongoing research, Martens already applies his software to study DNA repair in single-celled organisms. "I don't have a biological interpretation yet, but with my software, I can now – for the first time - follow the cell's repair kit minute by minute".