Research Areas
To cure disease, we need to understand how a healthy cell “works”. We know that the cell is a very complex biological system driven by the chemical interactions between DNA, RNA, proteins, and small organic and inorganic compounds. It would be impossible to study the cell as a whole but, what we can do, is to identify, within this complex system, a feature that we can focus on, comprehend at the molecular level and in a second stage use it as a “piece of the puzzle” to understand the entire system.
- How do cells divide? How is the genetic material correctly distributed between the two daughter cells?
- How do bacterial toxins infect host cells?
- How are genetic rearrangements in meiosis regulated?
- How is cell morphology regulated?
- How is the microtubule network regulated during cell division, cell migration and neuronal morphogenesis?
- How does a muscle contract?
- How does membrane fusion occur during sexual reproduction?
- What are the mechanisms that control chromatin dynamics?
- How does cell communication regulate cell fate decisions and cell identity?
- How is DNA replication initiated?
- What is the function and biogenesis of peroxisomes?
- How are DNA modifications translated into cellular responses?
- How can we synthesize small active organic compounds, similar to natural products? And how can we identify their target in cells?
These are a few of the many questions that our scientists are interested in.
APPROACHES
In modern biology, we choose the question that we are interested in and then we will use all the approaches possible to find the answers.
At the IMPRS-LM we use:
- Single Particle Cryo-Electron Microscopy (Cryo-EM)
- X-ray Crystallography
- NMR Spectroscopy
- Mass Spectrometry
- and many biophysical techniques (Ultra-centrifugation, Calorimetry, Surface Plasmon Resonance) to understand at the molecular level how bio-molecules interact, form a complex, are activated, transduce a signal, etc..
In addition to:
- Advanced Light Microscopy (Live cell Imaging, TIRF Microscopy, Spinning Disk Microscopy)
- Functional Imaging (FRET, FLIM, STED)
- and many combinations of the above to study localization, mobility, dynamics of active/inactive biomolecules and lifetimes of complexes of molecules in the cell.
As model systems, we use budding yeast, mammalian cell culture cells and stem cells but we also strongly believe that a very powerful way to fully understand a biochemical ensemble is to try to reconstitute in vitro its activity using a minimal set of components.
We aim, for example, to reconstitute “synthetic kinetochores”, or “synthetic histones” with different histones combinations or modification, or “synthetic membranes” with different lipid concentrations and membrane bound proteins. Once we can reconstitute a synthetic system we can ask very basic but fundamental questions: which are the minimal set of components to recapitulate the biological system we are studying? Which are the crucial interactions that determine the activity that we are studying? How does our system respond to perturbations?
What we learn from a minimal in vitro system, can then be tested in the complex environment of the cell or an organism.