Research group Erik Lindahl's research group

We use a number of techniques ranging from bioinformatics to build models of human receptors and channels based on bacterial structures, biomolecular simulations to understand the molecular-level interactions in these complex molecules, and experimental techniques such as electrophysiology or spectroscopy to measure functional effects of conformational transitions, and how these are influenced by mutations in the membrane proteins or small molecules that can work as medical drugs. For example, this has enabled us to use molecular models in combination with experiments to determine how voltage-gated ion channels move between intermediate states during opening (Henrion 2012, Lindahl 2012). Similarly, in our work on the ligand-gated ion channels responsible for transmitting signals across the synaptic cleft between nerve cells we have been able to show that there are separate binding sites for molecules that either potentiate (amplify) or inhibit the nerve signals (Murail 2012). We can even reverse the behavior of the these channels by introducing single-site mutations that force the molecule to bind in a different allosteric modulation site, which opens the door to design of pairs of drugs that could be used to control the nerve system on a very fine-grained level (Brömstrup 2013). Finally, we are using both simulations and experiments to study how ATPase pumps transport ions, which has led to the first-ever structures of pumps with bound ions (Nyblom 2013).

The team also works with molecular simulation methodology development, in particular the widely used GROMACS package for which we are steering an international development team (Pronk 2013, Abraham 2015).

Since the start of 2016, we are excited to help build the new national infrastructure and research platform around cryo-electro microscopy at Stockholm University. Structure determination with cryo-EM works by collecting tens of thousands to millions of extremely noisy 2D images of single molecules, and our work is focused on developing new better and faster methods to reconstruct three-dimensional electron densities from the noisy micrograph data, in particular for the program RELION (Kimanius 2016, Forsberg 2017).

Funding

Swedish Research Council, European Research Council, Knut & Alice Wallenberg Foundation, Strategic Research Area on E-Science, Science for Life Laboratory, Foundation for Strategic Research, Horizon-2020/EINFRA, National Institute of Health, Carl Trygger Foundation, Magnus Bergvall foundation, STINT, Computing resources through SNIC, and cryo-EM time through the SU-led facility at SciLifeLab funded by KAW and the Erling Persson foundation.