Research


The Applied Microbiology Research Lab is located at the Department Biomedicine, University of Basel.

  • Research Focus

Approximately 500’000 people get infected with influenza viruses in Switzerland every year. Worldwide, almost 1/5 of the global population is infected. Therefore, the annual influenza epidemic is associated with substantial health-care costs, high morbidity and mortality on a global scale. At highest risk for reduced clinical outcomes are young children, elderly people, pregnant women, and patients with chronic diseases such as diabetes or with prolonged immunosuppression. The primary strategy to prevent infection is through vaccination. However, the vaccine efficacy is poor in high-risk groups (O’ Shea et al. Curr Infect Dis Rep. 2014; Linnik JE, Egli A. Hum Vaccin Immunother. 2016). In addition, the factors influencing Influenza Transmission are highly complex and not only focused on the immune response.

We aim to explore (i) the host-pathogen interaction in more detail to understand transmission dynamics of influenza in the context of individual and herd immunity and (ii) geographical and temporal patterns of infection transmission including behavioural and social metadata.

In our research, we focus on transmission of infectious diseases and corresponding immunity in individuals, but also on a whole population level. A crucial factor in the immune response of a population is the genetic heterogeneity associated individal susceptibilities for infections and likelihoods for disease transmission. Interferons such as the Type I and III. IFNs have been associated with modulation of the adaptive immune functions, which is also highly crucial in the humoral immune response. IFN release is a rather early event in the immune response, following the recognition via so call Toll-like receptors. Genetic polymorphisms in the Interferon signalling cascade have been described to play crucial role in disease susceptibility (Syedbasha M, Egli A. Front Immunol 2017).

 

  • Transmission of pathogens

Dr. Helena Seth-Smith, Daniela Lang, Josi Reist, Aline Cuenod

In a series of Projects, we try to understand the dynamic of pathogen transmission in the hospital and public environement. In particular, virulence factors such as toxins may play a crucial role in bacteria such as methicillin resistant Staphylococcus aureus or Cornyebacterium diphtheriae (Meinel D.M. et al. CMI 2016; Piso R. J. et al. Plos one 2017). Some bacterial pathogens are part of the Environment and do only rarely lead to infections. However, in the case of Burholderia stabilis, a contaminated medical product was causing a Swiss wide series of infections (Sommerstein R et al. Eurosurveillance 2017). We use whole genome sequencing in order to have the highest potential resolution in order to compare single bacterial isolates within an outbreak. The combination with epidemiological, clinical and immunological metadata allows to build complex models of disease transmission.

In two NRP72 funded projects, we currently, try to understand the (plasmid) transmission of extended betalactamase producing Enterobacteriacea in the hospital and environment (collaborations with Dr. Sarah Tschudin-Sutter, USB and Prof. Sebastian Bonhoeffer, ETH Zurich).

In a SNF funded interdisciplinary grant,  we explore the spatiotemporal dynamic of influenza transmission in the City of Basel (https://www.bsse.ethz.ch/cevo/research/influenza-in-basel.html). In this Project, we sequence clinical strains and link the phylogeny to geographical and epidemiological metadata. This Project also includes a measurment of Influenza antibody titers in a group of healthy volunteers living in Basel, in order to Monitor herd immunity over time.

 

  • Humoral vaccine response in the context of IFN lambda

Mohammedyaseen Syedbasha and Janina Linnik

In this SNSF supported project, we explore how IFN lambda impacts on the humoral immune response. The project aims in explore mechanistical aspects in particular the signalling cascades affected by IFN lambda in various immune subsets and links this with B-cell functions and maturation.

We have recruited stem cell transplant recipients routinely vaccinated with a trivalent Influenza vaccine and measure the vaccine induced cellular and humoral immune response (cytokines, and antibodies). The activity of INF lambda signalling is determined and genetic polymorphisms are analyzed in the context of the immune response.

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  • Computational modelling of the IFN lambda signalling

Janina Linnik and Mohammedyaseen Syedbasha

In this SystemsX supported project, we try to develop a system biological computational model of the IFN lambda signalling cascade in immune cells. We aim to link the IFN lambda signalling with the induced immune response upon vaccination. The impact of single nucleotide polymorphisms in the signalling cascade is further explored.

signalling_network