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Naderer Lab research

CollaborationsStudent research projects | Publications

Our research

Current projects

Macrophages are the first line immune cells that destroy invading microbes and thus prevent infectious diseases. Several microbes, however, can hide within macrophages to cause disease. Our recent research, published in Nature Microbiology, has shown that drugs that kill infected macrophages prevent infectious diseases.

Several superbugs secret weapons to kill macrophages and to promote their own survival. In these cases, our research is focused in preventing macrophage death by targeting host factors with existing drugs to restore protective immunity.

We currently work on microbes that cause life-threatening pneumonia, systemic fungal infections and sexually transmitted diseases. We believe that understanding the macrophage-microbe interaction is key for the development of new treatment options.

1. Programmed cell death signalling in infections

2. Bacterial vesicles and toxins that target macrophages

3. Pathogen evasion of macrophage attack

4. Metabolic interactions between macrophages and microbes

Visit Dr Naderer's Monash research profile to see a full listing of current projects.

Research activities

1. Macrophage cell death signalling in infections

Macrophages are phagocytic (to engulf and digest) immune cells designed to kill invading microorganisms by employing a diverse arsenal of anti-microbial agents. They are part of the first line defence (innate immune response) but also initiate adaptive immunity. In the presence of persistent pathogen, macrophages induce programmed cell death pathway to release intracellular microbes and to activate other immune responses by releasing inflammatory cytokines. We study the role of the different forms of cell death, such as apoptosis, pyroptosis and necroptosis, in bacterial and fungal infections by using genetic approaches in mice and human macrophages.

Macrophages infected with GFP-expressing Legionella lose their mitochondrial potential (red) and succumb to infections (blue) over time.

2. Bacterial vesicles and toxins cause macrophage death

Bacteria, such as Staphylococcus aureus, Legionella pneumonia and Neisseria gonorrhoeae secrete toxins that target host cell death pathway to either prevent or induce macrophage death. We have recently shown that vesicles secreted by all bacteria and protein effector attack the mitochondria of macrophages and thus control several antimicrobial responses. We aim to discover how toxins traffic to mitochondria and which cell death pathways is activated or inhibited by these pathogens.

Mitochondria of macrophages (red) under attack by Neisseria vesicles (green) using super-resolution microscopy.

3. Pathogen evasion of macrophage attack

Several important human pathogens, including Legionella, Burkholderia, Mycobacteria and Leishmania survive long-term within specialized compartments or the cytosol of macrophages. Intracellular replication depends on hijacking host pathways to evade immunity and to establish a safe niche. We have shown that intracellular Legionella disarm macrophages by inhibiting host protein synthesis. We aim to exploit this to identify novel mechanism to activated host cell death pathway to eliminate intracellular microbes.

Macrophages infected with GFP-expressing Legionella (green) were labelled with Mitotracker Red and live-cells imaged with a high-resolution microscope (N-SIM, Nikon)

4. Metabolic interactions between macrophages and microbes

Metabolism is emerged as a key mechanism to firstly activated macrophages to mount antimicrobial responses but also to enable intracellular microbes to scavenge essential nutrients from host cells. We have recently shown that metabolic pathways of macrophages and microbes are intimately linked and that this can be harnessed for novel treatment options. We aim to identify new metabolic interactions between macrophages and microbes.

Techniques/expertise

Imaging

We use live-cell imaging with a fully automatic microscope to visualise individual macrophages and their microbes over extended periods of time. This enables detection of host cell activities on the single cell level and quantification of events.

We use super-resolution and electron microscopy to capture host-microbe interaction at the highest possible resolution. This enables us to visualise how microbial molecules attack mitochondria.

CRISPR

We use the Cas9/CRISPR gene editing system to generate knock out cells for the study of host factors in infections. To identify novel factors, we use CRISPR screens in macrophages to isolate clones that resist infections.

Stem cell technology

To study human macrophages, we have established induced pluripotent stem cells which can be differentiated to macrophages and other immune cells that mimicking tissue-resident cells. We are using CRISPR technology to generate mutant human macrophages and to identify host pathways that promote or inhibit infections.

Proteomics
Metabolomics
Bacterial mutagenesis
Molecular and Biochemical assays

Disease models

Pneumonia (Legionella, S. aureus)
Gonorrhoea (Neisseria)

Collaborations

We collaborate with many scientists and research organisations around the world. Some of our more significant national and international collaborators are listed below. Click on the map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).

  • Ana Traven (Monash University)
  • James Vince (WEHI)
  • Kate Lawlor (Hudson Institute)
  • Gordon Dougan (Cambridge University, UK)
  • Michael Lazarou (Monash University)
  • Anton Peleg (Monash University)
  • Mei-Ling Gao (Wenzhou Medical University, China)
  • Trevor Lithgow (Monash University)
  • Liz Hartland (Hudson Institute)
  • Carmen Buchrieser (Pasteur Institute, France)
  • NHMRC Program in Cellular Microbiology
  • Unit for Host-Pathogen Molecular Biology
  • Monash Micro Imaging Platform

Student research projects

The Naderer Lab offers a variety of Honours, Masters and PhD projects for students interested in joining our group. There are also a number of short term research opportunities available.

Please visit Supervisor Connect to explore the projects currently available in our Lab.