Host
Prof. Dr. Michael Meyer-Hermann
Department of Systems Immunology
HZI, Braunschweig, Germany
Duration 36 months
 
Agent-based modelling of affinity maturation and germinal centre shutdown
 
Background
Germinal centres (GC) are small spatially and functionally structured micro-organs supporting the development of high-affinity antibodies by B cells. Activated B cells develop high-affinity antibodies in an evolutionary process called affinity maturation. They undergo multiple rounds of selective mutation of the B cell receptor/antibody (somatic hypermutation) and are selected towards those with the highest affinity. GC are fundamental to all humoral immune responses and their malfunction or failure to initiate a GC reaction has been implicated in numerous pathological conditions, ranging from poor vaccination responses in certain patient cohorts to autoimmune diseases like rheumatoid arthritis and B cell lymphoma.
 
Approach
An agent-based, spatially resolved model of the GC reaction has been developed in our team. The model includes a detailed description of key processes for spatial and functional properties of germinal centres such as movement of B cells along gradients of diffusable substances, competition for antigen, proliferation and death of B cells, and interaction with T cells. The model has been developed and validated in close collaboration with experimental partners and accurately reproduces relevant properties of the affinity maturation process. You will develop and extend this model with a strong focus on clinical challenges; specifically, you will implement putative disease mechanisms for the involvement of GC in B cell lymphoma and rheumatoid arthritis and evaluate these hypotheses based on experimental data.
 
Our department
The department, founded only 7 years ago and constantly growing, is working on mathematical modelling of immunological systems. Our methodology is as diverse as our individual backgrounds: researchers from physics, mathematics, computer science, engineering, and biology work together using methods from ODE- and PDE systems to agent-based models. This diversity covers a wide range of applications, including adaptive immunity, chronic and acute inflammation, bacterial and viral diseases, electrophysiology, embedded in a large campus for experimental research.
 
Your profile
We are looking for a highly motivated, creative open mind, able to develop and shape the project with own ideas. Applicants with education in mathematics, computer science, physics, engineering, or related fields are welcome to apply. Experience in the development of mathematical models and at least basic knowledge of differential equations (ODE and/or PDE) is a requirement; experience with agent-based models is a bonus, but can be learned in our department. Skills in model calibration, programming with C++, visualization of results, and working in a Linux environment are a plus.
 
Our offer
This position is funded by the Marie Skłodowska-Curie actions of the European Union's Horizon 2020 research and innovation programme under grant agreement No 765158.  The appointment is with AMC Medical Research (AMR), Amsterdam, The Netherlands. Under recruitment procedure the general MC salary description is detailed. Due to local law and differences in family situation, the exact salary will be determined in the host institution upon recruitment.
 
Your application
See recruitment procedure. You can apply using the online application form. For more information about the position you can contact Prof. Dr. Michael Meyer-Hermann (jobs@theoretical-biology.de).

 

© 2018 COSMIC. All Rights Reserved.

Please publish modules in offcanvas position.