System-Immunologie
Das Immunsystem mit Hilfe der Mathematik zu verstehen, das ist das Ziel der Abteilung System Immunologie. Mathematische Modelle sollen helfen, Krankheiten schneller und besser zu erforschen, die mit dem Immunsystem in Verbindung stehen. Erfahren Sie hier, wie die Forscher die Mathematik nutzen, um chronisch-entzündliche Krankheiten, die Steuerung von speziell auf Erreger angepasste Immunantworten sowie die Wechselwirkung des Nerven-, des endokrinen und des Immunsystems zu untersuchen.
Leitung
Forschungsprojekte
Viral dynamics
The dynamics of the interplay between virus and immune system depend not only on the mutating virus but also on the responsiveness of the immune system of each individual patient. We investigate critical parameters for the control of viral infections, paving the ground for a more personalized therapy of viral infections.
Understanding and controlling the immune response to influenza with cytokine networks
Most models of immune responses to influenza are based on cell interactions. We show that we can understand host-pathogen-interactions based on cytokine network and apply this technique to optimize therapies of influenza infections. More
How does ageing affect the immune response to influenza infections?
We show that weak immune responses to influenza in old individuals is related to a slow viral replication in infected cells inducing a subcritical immune stimulus rather than to an inefficient immune system. More
When to start and switch treatment in HIV infection?
By optimizing a mathematical model for HIV infections, we predict that early therapy initiation within 2 years post infection is critical to delay disease progression to AIDS. More
Bacterial infections
With the help of mathematical models, we aim at identifying mechanisms of bacterial immune evasion and protection against antibiotics.
Mechanisms of adaptation of Pseudomonas aeruginosa
We determine mechanisms of biofilm formation with spatio-temporal agent-based simulations and identify critical parameters suitable for in vivo manipulation preventing the spread of Pseudomonas aeruginosa infections. More
Strategies of Borrelia to evade immune responses
Borrelia is a tick-borne infection with long lasting, severe symptoms. By modeling its within-host population dynamics, we identified how the bacteria survive the strong first immune response. More
Interaction of microbiota and immune system
With the help of in silico simulations, we determine modes of interactions between gut microbiota and the immune system that control the microbiota composition as well as the inflammatory state of the individual. More
Antibody responses
Efficient immune responses against pathogens and vaccination success depend on the generation of high affinity antibodies. These are generated in an evolutionary process in germinal centre reactions. We employ computer simulations to understand the mechanisms of germinal centre induction, B cell selection, affinity maturation, B cell differentiation, and germinal centre shutdown.
Selected germinal centre B cells recycle to a re-dividing phenotype
Our in silico prediction that recycling is the dominant fate of selected B cells is now confirmed with an elegant photoactivation experiments. More
Transient chemotaxis sensitivity model of germinal centre B cells
Based on two-photon imaging data on B cell motility we showed with spatial mathematical models of cell motility that germinal centre B cells only transiently acquire sensitivity for chemokines and do random walk most of the time. More
T cell help is the limiting factor of germinal centre B cell selection
We revised the old-standing paradigm that the limiting factor driving affinity maturation in germinal centres is antigen presentation. From the assumption that evolution would develop the most efficient mechanism of affinity maturation, we derived the prediction that the interaction with follicular helper T cells is the limiting factor of B cell selection. More
Ways to optimise quality and quantity of antibodies
Our mathematical models show that affinity-dependent number of divisions induced in positively selected B cells can improve the quantity and the quality of germinal centre derived plasma cells. More
Do germinal centres interact via their produced antibodies?
We showed that antibodies generated by the germinal centre re-enter germinal centres, influence the affinity maturation process, and are essential for the shut-down of germinal centre reactions. More
Innate immunity supports the initiation of germinal centre reactions
We have shown that factors associated with innate immunity are also critical for germinal centre formation. More
What controls the initiation of tertiary lymphoid tissue?
Lymphoid tissue can develop in ectopic places and contribute to disease progression. We investigate early diagnostic signatures of tertiary lymphoid tissue formation in order to prevent, for example, rejection of the renal transplant by adapted treatments. More
T cell responses
T cells are essential players of cytotoxic immunity, support innate and humoral immunity against pathogens, and are main regulators of auto-immunity. We developed theories to unravel the necessary conditions for homeostasis of a functional and self-tolerant T cell repertoire, we employ mathematical models for the processes of thymic selection, peripheral homeostasis, and immune activation of T cells in the context of infection and autoimmunity.
A signal integration model for thymic selection
We developed the first mathematical model of thymic selection based on the time-integration of signals from multiple interactions. We developed a novel theory of how a functional T cell receptor repertoire is shaped in the thymus. More
How are regulatory T cells maintained in the immune system?
Based on detailed measurements of regulatory T cell reconstitution, we derived unexpected T cell subset specific migration properties between organs. With a multi-organ model of the T cell compartment, we derived the frequency of conversion from naïve to regulatory T cells. More
Analysis of the role of trans-membrane molecules for T cell calcium dynamics
A mathematical model for T cell calcium electrophysiology predicts that Calcium Release-Activated Channels supports a long-term sustained calcium enhancement rather than short-term calcium increases. More
A quantitative concept of self-nonself distinction
We proposed a theory for immune tolerance versus activation without a distinction of immune stimulation by self and nonself molecules. More
Intra- and inter-cellular-trafficking
It is becoming more and more evident that the spatial organization of organelles and molecules within a cell is essential for its functionality. In view of available intracellular imaging technologies providing a firm data basis, we develop spatial multi-scale mathematical models for intracellular dynamics and connect spatial distributions of molecules to signalling and function.
Information processing via immunological synapses
With an agent-based model for the dynamics of the formation of immunological synapses, we uncover principles of information processing in adaptive immune responses. More
A thief of co-stimulation controls T cell activation
CTLA4 on T cells binds co-stimulatory molecules on antigen presenting cells and steals them by a process called transendocytosis. We determine the potential of this process in controlling T cell activation. More
Inducing synchrony of coupled excitable cells by noise
We show how stochastic variation in the expression profile of coupled excitable cells can synchronize the activity of the cells and, by this, ensure the functionality of the organ. More
Spatio-temporal organization of the mitochondrial reticulum and quality control
Mitochondria quality control is a persistent process involving reorganization of the mitochondrial network. We found that cells act around a percolation threshold of tip-to-side mitochondria fission/fusion rates, at which the reticulum network switches between a fully disconnected and a fully connected network. More
Organization, motility, and age of intracellular insulin granules
A 3D model for the dynamics of insulin biosynthesis, transport and exocytosis shows how newly synthesized insulin carrying granules boost through the cytosol and are released faster than old granules at the plasma membrane. More
Systemic interactions
The interactions between the nervous, the endocrine, and the immune system is not well understood but bears a great potential of improving human health and medical treatments.
Optimising cortisol therapy with a clock
Cortisol, if given in the late evening, has a three-fold higher efficiency in controlling pro-inflammatory factors. More
Optimizing cancer therapies in silico
We developed irradiation schedules that optimize the efficiency of cancer treatment. More
Inflammation signals in type 2 diabetes
The pro-inflammatory molecuIe IL-1beta is a switch parameter for onset of type II diabetes. We propose a treatment schedule targeting IL-1beta and explain the failure of clinical trials targeting pro-inflammatory factors. More
Individualised infection medicine
The potential of improving disease control by including individual parameters in treatment decisions is acknowledged but far from clinical reality for most diseases. Mathematical models can help to explore this big potential.
Cytokine response to Ebola virus
A model for cytokine response to Ebola virus predicts key differences in the immune response between survivors, fatalities and asymptomatic infections. More
Optimising oseltamivir dosing and schedule for individual influenza patients
Based on measurements of immune effector cells and viral load, we develop a feedback controller that adaptively predicts the optimal treatment dose and schedule for individual patients. More
Restoring influenza vaccination success in poor responders
We employ stochastic and agent-based mathematical models as a tool to predict the optimal vaccination strategy according to immune parameters easily measured from individuals. More
Quantitative methods in systems immunology
The success of mathematical models in biology and medicine mostly relies on a deep knowledge of the biological system and the disease and the right level of abstraction. However, the right methodology and high-standards in simulation techniques are also required. We contributed to a number of methodological developments.
Discrete agent-based models
We developed HYPHASMA (greek for tissue) as a modelling platform for interacting cells with a subcellular resolution. More
Lattice-free agent-based models and Delaunay-Object-Dynamics
Delaunay-Object-Dynamics is a new modelling strategy that combines cell geometry with the philosophy of Molecular Dynamics. More
Differential equations, parameter fitting, and identifiability analysis
We invented an iterative strategy for parameter estimation based on the idea of decomposing a complex problem into simpler subsystems. More
LOKI-Pandemics
LOKI-Pandemics ist ein Pilotprojekt, welches durch die Helmholtz-Gesellschaft gefördert wird. Innerhalb des Projektes wird die Plattform ESID (Epidemiological Scenarios for Infectious Diseases) zur lokalen Kontrolle von Infektionsausbrüchen in Zusammenarbeit mit Pilot-Gesundheitsämtern entwickelt. In dieser Plattform werden regionale mathematische und agentenbasierte Modelle, welche modular aufgebaut sind, über einen Mobilitätsgraphen verknüpft und Methoden des maschinellen Lernens verarbeitet. Das Projekt LOKI-Pandemics besteht aus verschiedenen Teilprojekten, in denen Expert:innen unterschiedlicher Fachrichtungen gemeinsam an der Entwicklung und Umsetzung der Plattform arbeiten. Daher kollaboriert das HZI hier mit dem DLR, CISPA, UFZ und FZJ sowie mit der Akademie für öffentliches Gesundheitswesen. Die Ziele sind es Pandemien und Ausbrüche auf lokaler Ebene frühzeitig zu erkennen und deren Ausbreitung lokal zu überwachen. Außerdem geht es um eine umfassende Bewertung der Situation durch Simulation von Szenarien mit und ohne Maßnahmen sowie um eine Optimierung unter realen Bedingungen.
Weitere Informationen zu dem Projekt finden Sie auf der Homepage von LOKI-Pandemics: LOKI-Pandemics
