s

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Martin Lochner

Ion channels are transmembrane protein complexes which allow passage of ions through biological membranes. Their functions are essential for numerous physiological processes and they work as complex molecular machines that can conduct ions with excellent specificity, in huge quantities, at great speeds, under very tight regulation. Ligand-gated ion channels for instance, are activated by small molecules (i.e. ligands) and responsible for the fast transmission of nerve impulses at the synapse and the neuromuscular junction. Due to their important functional role and known mutations linked to many human diseases ion channels are attractive targets for drug therapy.

Transmembrane proteins, including ion channels and transporters, are notoriously difficult to crystallize and it remains challenging to solve their exact three-dimensional structure by X-ray. Undoubtedly, decades of mutagenesis and electrophysiology studies, together with structural biology efforts, have made critical contributions to our understanding of ion channels and transporters. Nevertheless, these methods have clear limitations and tailor-made small bioactive compounds decorated with fluorescent, photoaffinity and/or affinity tags are emerging as complementary research tools for cellular investigations of ion channels and transporters.

The Lochner group combines expertise in synthetic organic chemistry and neurochemistry, in particular focusing on ligand-gated ion channels. The overall aim is to design and synthesize small molecular tools based on known high-affinity compounds in order to investigate the structure and function of ion channels, but also to facilitate their chemical modification. In the last few years the group has synthesized molecular probes for the serotonin 5-HT3 receptor by appending fluorescent tags (BODIPY, coumarin, dansyl and NBD) and photoaffinity tags (diazirine, benzophenone, aryl azide) to a known 5-HT3 receptor antagonist (J. Med. Chem. 2010, 53. 2324). These probes show nanomolar affinities towards the human 5-HT3 receptor and are currently evaluated as tools for the cellular study of this receptor (in collaboration with the Lummis group, Cambridge, UK). The interdisciplinary and innovative approaches have recently been recognized by the award of a SNSF-professorship to Martin Lochner.

Current projects focus on more sophisticated probes for the 5-HT3 receptor and novel molecular tools for the study of the cardiac K+ channel hERG (in collaboration with the Abriel group, Dept. Clinical Research, Bern). We are about to embark on a new project concerning the design and synthesis of molecular probes for the investigation of glutamate transporters.

Personal Website:
Lochner Group

E-Mail:
martin.lochner@dcb.unibe.ch

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Function in NCCR

  • Principal Investigator (PI)

Intern/Extern: Intern

Projects

Workgroup:
Lochner Martin

2010-now 
SNF-Professor, Department of Chemistry and Biochemistry, University of Bern

Education

  • 2003  Ph.D. in Chemistry at the University of Basel
  • 1998  M.Sc. in Chemistry at the University of Zurich

Selected memberships

  • Royal Society of Chemistry
  • Swiss Chemical Society

Selected awards

  • Award of a SNF-Professorship in the area of Chemical Biology (2009)
  • Recipient of a first grant award from the UK Engineering and Physical Sciences Research Council (EPSRC) to support interdisciplinary research (2007)