Infection, Inflammation and Autophagy

Infection, Inflammation and Autophagy

Cells frequently experience stress resulting in activation of PRR responses and induction of autophagy, a process that is essential for cellular homeostasis and, if defective, leads to disorders like degenerative diseases, cancers, infections, inflammation and cardiovascular disease

We aim to define novel relations between oxidative stress, signalling through PRRs and autophagy in inflammatory diseases, including mycobacterial and HIV infections where the focus is molecular host defence mechanisms involved in immunity to mycobacteria and HIV, and virulence strategies employed by these pathogens to parasitize host cells.

Major achievements

  1. Established the role of Lipocalin 2 in urinary tract infection.
  2. Established the role of Keap1 as a negative regulator of inflammatory signalling in M. avium infected primary human macrophages.
  3. Established that TLR7 and 8 recognize mycobacterial and HIV RNA and induce inflammatory responses from macrophage and T-cell intracellular compartments.
  4. Established correlative imaging of infected macrophages at an ultra-high resolution and in 3D using FIB-SEM tomography together with confocal fluorescence microscopy.
  5. Established a method for benzoic acid-inducible gene expression in mycobacteria.
  6. Established that a novel antimycobacterial compound acts as an iron chelator and identified novel proteins involved in iron metabolism in M. tuberculosis.
  7. Established dynamics of M. avium infection in mice and infection models and routines for working with HIV and Mtb in new BSL3 labs.
  8. Identified intra-patient mutations in M. avium and established phenotypic differences between the strains.
  9. Established an assay for protein secretion by the M. tuberculosis ESX-3 secretion system (for use in drug screens targeting ESX-3).
  10. Established the role of lipid metabolism in HIV disease susceptibility and progression.
  11. Established that n-3 polyunsaturated fatty acids protect retinal epithelial cells from harmful stress by inducing autophagy and oxidative stress defences.
  12. Established that the moderate oxidative stress induced by physiologic concentrations of omega-3 fatty acids is toxic to cancer cells with downregulated autophagy.
  13. Established that n-3 polyunsaturated fatty acids in a lipid selective manner dampen LPS induced pro-inflammatory signalling in macrophages.
  14. Established that myeloma cells use different resistance mechanisms towards reversible and irreversible proteasome inhibitors.
  15. Founded a basis for identification of novel ATP-competitors targeting macrophage activation.
  16. Developed an approach to quantify PI3K signaling in tumour sections obtained prior to and after targeted therapy and correlated the changes with effects on tumour metabolism using MR.

A macrophage infected with Mycobacterium avium was imaged in 3D using a Focused Ion Beam/Scanning Electron Microscope (FIB/SEM) at NTNU Nanolab. Photo

11 Jun 2018