SNIC
SUPR
SNIC SUPR
Membrane fusion, permeability, and infectious disease
Dnr:

SNIC 2018/2-8

Type:

SNAC Large

Principal Investigator:

Peter Kasson

Affiliation:

Uppsala universitet

Start Date:

2019-01-01

End Date:

2020-01-01

Primary Classification:

10603: Biophysics

Secondary Classification:

30109: Microbiology in the medical area

Tertiary Classification:

10402: Physical Chemistry

Allocation

Abstract

This project supports two research areas in the membrane biophysics of infectious disease. The first is influenza viral entry; we are studying how influenza proteins interact with membranes to achieve fusion and how mutations to these proteins or changes to the membrane composition can affect this process. Simulation data are combined with single-virus fusion experiments performed in our laboratory. The second is antibiotic uptake by gram-negative bacteria. Many small-molecules are effective against purified bacterial targets but fail in live bacteria; one major reason for this is the uptake properties of the bacterial membranes and transporters. We have developed a moderate-throughput simulation protocol that can predict antibiotic uptake rates significantly better than state-of-the-art methods. We are prospectively validating these predictions against experiments performed in our laboratory and then plan to use this approach to guide optimization of new small molecules for better bacterial uptake.