Projects

Translocation Transfer

Mathias Winterhalter

Affiliation:

Jacobs University Bremen
28759 Bremen
Germany

Contact:

Phone: +49 421 200 3248,
Email: m.winterhalter@jacobs-university.de
Website: http://winterhalter.user.jacobs-university.de 

Key words:

Porin, transport, electrophysiology

Expertise:

biophysics, characterization of porins, electrophysiology, molecular transport

Our main interest is on the development of tools to quantify transport of small molecules (antibiotics, nutrients…) across porins and thus gaining a molecular understanding of these transport processes. We produce porins, modify them by mutation or chemically and reconstitute them into planar lipid bilayer und analyse the ion current fluctuation in presence of small molecules to obtain information on permeation. The team is embedded in a local network at Jacobs comprising computational biophysics (all atom modelling of transport, U. Kleinekathöfer), Chemistry (D. Gabel), experimental biophysics, electrophysiology (transport characterization through channel, R. Benz, R. Wagner, M. Winterhalter). During the recent 6 years we were the academic leader of Translocation (IMI-New Drug For Bad Bugs).

References:

  • Vergali,J., et al.. Porins and small-molecule translocation across the outer membrane of Gram- negative bacteria. Nat. Rev. Microbiol. (2019) in press.
  • Wang, J.J. et al. Electrophysiological characterization of transport across outer membrane channels from Gram-negative bacteria in their native environment. doi.org/10.26434/chemrxiv.8282204.v2
  • Wang J, et al. Small molecule permeation across membrane channels: Chemical modification to quantify transport across OmpF. Angewandte Chemie Int Ed. 58 (2019) 4737-4741.
  • Bhamidimarri SP, et. al. A Multidisciplinary Approach toward Identification of Antibiotic Scaffolds for Acinetobacter baumannii.Structure. 27 (2019) 268-280. doi: 10.1016/j.str.2018.10.021
  • Dumont et al..Mechanistic aspects of maltotriose-conjugate translocation to the Gram-negative bacteria cytoplasm. Life Sci Alliance.2 (2018) e201800242.doi:  10.26508/lsa.201800242.
  • Glenwright AJ, et al. Structural base for nutrient acquisition by dominant members of the human gut microbiota. Nature 541 (2017) 407-11.
  • Acosta-Gutierrez S, et al. Getting drugs into Gram-negative bacteria: Rational rules for permeation through general porins. ACS Infect Dis. 4 (2018) 1519-1528. doi: 10.1021/acsinfecdis.8b00149.
  • Samanta, S. et al. Getting Drugs through Small Pores: Exploiting the Porins Pathway in Pseudomonas aeruginosa. 4 (2018) 1487-1598.
  • Soundararajan G, Bhamidimarri, SP, Winterhalter M. Understanding carbapenem translocation through OccD3 (OpdP) of Pseudomonas aeruginosa. ACS Chemical Biology 12 (2017) 1656-64.
  • Stavenger RA, Winterhalter M. How to get good drugs into bad bugs. Science Transl. Med. 6 (2014) 228ed7.