Dr Andreas Lengeling

The Roslin Institute

Research Interests

Infectious diseases of livestock and humans are a great threat to human welfare, and sustained global economic and social development. To combat infectious diseases it is necessary to understand the interaction between hosts and pathogens as well as the nature of host immune responses that provide protection to infections and associated mechanisms of disease resistance. Such knowledge can be used to develop novel strategies for the prevention and control of animal and human infectious diseases. In this area the research in my lab is centred on three major topics:

1) Genetic basis of host susceptibility to infection

Host susceptibility to infectious diseases and inflammatory disorders is under complex genetic control. We are using the mouse as an animal model to study pathogenesis mechanisms during infection and to identify genes that affect susceptibility to infectious diseases. This approach consists of identifying initial differences in host resistance to a specific pathogen amongst different inbred strains of mice. Genetic crosses between inbred strains that display large differences in host resistance are then used to map quantitative trait loci (QTL) that underlie these phenotypes. Using such an approach we have mapped three QTL loci on mouse chromosomes 2, 7 and 17 which determine resistance to Group A Streptococci in mice (Medina et al., J. Infect. Dis. 2001; Goldmann et al., J. Immunol. 2005, Medina and Lengeling, Brief. Funct. Genomic Proteomic. 2005).

2) Development of new animal models for veterinary and human infectious diseases

The host tropism and virulence of a specific pathogen has usually co-evolved with its host. This host specificity is determined by a complex interaction of host and microbial factors. There are many examples how this has prevented or limited the development of appropriate mouse models for infectious diseases. My laboratory has taken in the past an approach which we call 'pathogen murinisation'. This means that a pathogen is adapted to the murine host via genetic modification of key virulence factors that then allow the study of host responses and mechanisms of infection in a previously inaccessible host. This has enabled us to develop a new mouse model for orally acquired listeriosis (Wollert et al., Cell 2007, Bergmann et al., BMC Microbiol. 2013). The mouse as an animal model system provides the genetic tools and reagents that can be used to dissect complex genetic networks and to identify causal mechanisms of gene actions. From human diseases there are numerous examples how mice have been instrumental for providing a deeper understanding of mechanisms that underlie disease pathogenesis. Through orthologous relationship of genes and pathways it is often possible to identify conserved mechanisms that are linked with disease development in different species. A goal of my laboratory is to contribute in novel ways to the development of new mouse models for zoonotic and infectious diseases of important livestock species. This is done in collaboration with other research groups at the Roslin Institute (Prof. David Gally and Prof. Ross Fitzgerald).

3) Role of macrophages in host defence and control of inflammation

To fight infections macrophages are highly adapted to function in tissues under extreme oxygen-limiting conditions (hypoxia). We have recently shown that the jumonji-domain containing protein 6 (Jmjd6) is an oxygen-dependent regulator of alternative splicing. Jmjd6 expression is upregulated in hypoxic and inflammatory activated macrophages suggesting that Jmjd6 controls gene expression in response to danger signals such as oxygen stress and inflammation. To analyse the function of Jmjd6 under such conditions we have generated transgenic mouse lines to study effects of Jmjd6 deficiency in different immune cells and different stages of infection. Our aim is to identify new functions of Jmjd6 in the mouse and to use then comparative biology to test the wider relevance of such functions in other species.

Selected Publications

  • Silke Bergmann, Pip Beard, Bastian Pasche, Stefan Lienenklaus, Siegfried Weiss, Cormac G Gahan, Klaus Schughart, Andreas Lengeling. 2013. Influence of Internalin A murinisation on host resistance to orally acquired listeriosis in mice. BMC Microbiology Vol: 13. More»
  • Amin Tahoun, Simmi Mahajan, Edith Paxton, Georg Malterer, David S Donaldson, Dai Wang, Alwyn Tan, Trudi L Gillespie, Marie O'Shea, Andrew J Roe, Darren J Shaw, David L Gally, Andreas Lengeling, Neil A Mabbott, Juergen Haas, Arvind Mahajan. 2012. Salmonella transforms follicle-associated epithelial cells into M cells to promote intestinal invasion. Cell Host and Microbe Vol: 12 Pages: 645-56. More»
  • Thomas Wollert, Bastian Pasche, Maike Rochon, Stefanie Deppenmeier, Joop van den Heuvel, Achim D Gruber, Dirk W Heinz, Andreas Lengeling, Wolf-Dieter Schubert. 2007. Extending the host range of Listeria monocytogenes by rational protein design. Cell Vol: 129 Pages: 891-902. More»
  • Celia J Webby, Alexander Wolf, Natalia Gromak, Mathias Dreger, Holger Kramer, Benedikt Kessler, Michael L Nielsen, Corinna Schmitz, Danica S Butler, John R Yates, Claire M Delahunty, Phillip Hahn, Andreas Lengeling, Matthias Mann, Nicholas J Proudfoot, Christopher J Schofield, Angelika Böttger. 2009. Jmjd6 catalyses lysyl-hydroxylation of U2AF65, a protein associated with RNA splicing. Science Vol: 325 Pages: 90-93. More»
  • J.N. Boeckel, V. Guarani, M. Koyanagi, T. Roexe, A. Lengeling, R.T. Schermuly, P. Gellert, T. Braun, A. Zeiher, S. Dimmeler. 2011. Jumonji domain-containing protein 6 (Jmjd6) is required for angiogenic sprouting and regulates splicing of VEGF-receptor 1. Proceedings of the National Academy of Sciences Vol: 108 Pages: 3276-3281. More»