Physiological Systems

Sensory Physiology

How do the sensory neural circuits transform physical signals from outside world to neural signals that the brain could understand? This fundamental neural coding problem is the gate to understand our brain. By constructing multi-scale biophysical models that could reproduce the signal mapping performed by a population of neurons in different sensory systems, we aim to a) understand the sensory signal coding process; b) investigate whether there are general principles that govern the signal transformation across different sensory modalities.

 

Immune System

  

Immunodominance lies at the heart of the immune system's ability to distinguish self from non-self. Understanding and possibly controlling the mechanisms that govern immunodominance will have profound consequences for the fight against several classes of diseases, including viral infections and cancer.

  

 

Tissue homeostasis and cancer

There are a wide raft of computational models described in the literature, which represent numerous biological processes, and a key question encountered whenever investigating biological phenomena is: “What is the best way to model a biological process to answer a particular question?” Even if the appropriate modelling framework is known, a simulation able to investigate underlying principles or to make clinically relevant predictions will require the development and integration of numerous sub-models into a comprehensive spatiotemporal simulation. Moreover, in order to demonstrate that results produced from such simulations are not dependent on implementation of specific methodologies, the models should be implemented in a consistent and coherent manner. This project is concerned with using such techniques to answer questions to do with the development and maintenance of tissues, including when things go wrong.

Respiratory Modelling

Asthma and chronic obstructive pulmonary disease (COPD) are
common chronic diseases associated that affect over 500 million people worldwide. The diseases
are associated with significant disability and societal
burden, with related costs exceeding euro 56 billion per year in the European Union (EU) alone.
Asthma and COPD are complex airway diseases encompassing several underlying pathological
conditions and current therapies are inadequate owing to our incomplete understanding of the
diseases’ pathophysiology

We are interested in developing integrated models of lung ventilation, bringing together clinical data and computational models from a variety of scales to help understand the complex mechanisms behind asthma and COPD. This work is funded by and forms part of the Airway Disease Predicting Outcomes through Patient Specific Computational Modelling (AirPROM) project.

Cardiac Modelling

Computational modelling of the heart is now recognised as a powerful technique in the detailed investigation of cardiac behaviour. One of the major contributions of computational approaches to cardiovascular research has been the ability to dissect various effects and to tease out important relations between parameters, which are not possible using current experimental techniques. Recently, advanced computer models of cardiac electro-mechanical activity have been developed. The electrical properties of the myocardium are generally described by the bidomain equations, a set of coupled parabolic and elliptic partial differential equations (PDEs) that represents the tissue as two separate, distinct continua - one intracellular and the other extracellular. The intracellular and the extracellular media are connected via the cell membrane, and thus the two PDEs are coupled at each point in space through a set of complex, non-linear ordinary differential equations (ODEs), which describe the ionic transport across the cell membrane.

Vascular remodelling

Blood vessels are under constant mechanical load from blood pressure and flow. Changes to tissue stress distributions can disturb biochemical homeostasis and lead to vascular remodelling and possible dysfunction. How vessel walls sense and translate changes in mechanical load remains a central topic of mechanobiology. It has been suggested that the development of pathologies such as cerebral aneurysms or restenosis following angioplasty is related to this disturbance.

We are interested in developing integrated models of vascular remodelling by coupling HemeLB haemodynamics with models of cell migration and proliferation in Chaste. We believe that these models will increase our understanding of how the previous pathologies initiate and evolve.

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