Maximiliano Gutierrez: Projects

The host perspective: understanding phagosome biology and immune control of phagosome maturation

Figure 1

Figure 1- Spatio-temporal analysis of host factors associated with mycobacterial phagosomes. Adapted from Kasmapour et al., Proc. Natl. Acad. Sci USA (2012).

The aim of our research is to understand how host factors facilitate mycobacterial killing. The exact mechanisms that govern this initial sterilising reaction are not completely understood. Understanding therefore how host cells eliminate mycobacteria is important to find possible therapeutic strategies that enhance this natural response.

We have identified a large number of novel membrane trafficking factors regulated during the killing of mycobacteria by macrophages. We aim to define the function of these host factors during phagosome maturation and evaluate the impact on the innate immune response to M. tuberculosis. We expect that the knowledge emerging from our studies will identify critical host anti-mycobacterial factors. The characterisation of those factors will highlight attractive targets subverted by intracellular mycobacteria and new strategies to combat tuberculosis.

Selected publications

Kasmapour B, Gronow A, Bleck CKE, Hong W and Gutierrez MG. Size-dependent mechanism of cargo sorting during lysosome-phagosome fusion is controlled by Rab34 (2012) PNAS 109: 20485-90

Pei G, Bronietzki M, Gutierrez MG. Immune regulation of Rab proteins expression and intracellular transport (2012) J Leukoc Biol 92(1): 41-50

Bronietzki M, Kasmapour B, Gutierrez MG. Study of phagolysosome biogenesis in live macrophages (2014J Vis Exp 10: 85 Pei G, Repnik U, Griffiths G, Gutierrez MG. Identification of an immune regulated phagosomal Rab cascade in macrophages (2014) J Cell Sci 127: 2071-82

The pathogen perspective: understanding adaptation to host cell environments

Figure 2

Figure 2: Accumulation of neutral lipids in lipid droplets of intracellular mycobacteria. Adapted from Vazquez et al., Cell Microbiol 2014.

There is a significant lack of in vitro and in vivo tools to study the dynamics of M. tuberculosis adaptation to an intracellular environment and which factors are involved in this process. To overcome this problem, we are generating genetically modified M. tuberculosis strains that express different fluorescent reporters. These fluorescent reporters are being developed with the aim to provide spatio-temporal information of the environmental changes that bacteria face and which bacterial factors are switched on/off in response to these fluctuations. This genetic approach, combined with live cell imaging and in vivo studies, will facilitate the identification and characterisation of bacterial factors that contribute to M. tuberculosis pathogenesis.

We also established an in vitro cell-based model of long-term infection that considers one of the most important aspects of mycobacterial lifestyle: intracellularity. In our group, we are developing, characterising and validating this model as a new dynamic system to address questions in the field of mycobacterial adaptations to host cells. For that, we combine live cell imaging and phenotypic analysis to provide insights into the mechanism of mycobacterial adaptations. We also aim in the future to exploit this cellular system as a validated and predictive platform to find new effective chemical compounds against long-term intracellular mycobacteria. Our goal is to translate these concepts to more complex (and still imperfect) animal models to develop new therapies against latent infection.

Selected publications

Vazquez CL, Kasmapour B, Pei G, Gronow A, Bianco MV, Blanco FC, Bleck CKE, Bigi F, Abraham WR, Gutierrez MG. Experimental selection of long-term intracellular mycobacteria (2014Cell Microbiol 16(9): 1425-40.

 

Maximiliano Gutierrez

max.g@crick.ac.uk
+44 (0)20 379 61460

  • Qualifications and history
  • 2002 Biochemistry Degree, Universidad Nacional de San Luis, Argentina
  • 2003 Research Visitor, University of New Mexico, USA
  • 2004 Research Visitor, European Molecular Biology Laboratories (EMBL), Germany
  • 2005 PhD in Biochemistry, Universidad Nacional de Cuyo, Argentina
  • 2006 Post-Doctoral Fellow, European Molecular Biology Laboratories (EMBL), Germany
  • 2009 Junior Group Leader, Helmholtz Centre for Infection Research (HZI), Germany
  • 2012 Programme Leader Track, Medical Research Council National Institute for Medical Research, London, UK
  • 2015 Group Leader, the Francis Crick Institute, London, UK