Time: 11:00 AM Friday October 8th

Presentations (still preliminar order):

Modification of aneurysm development by chemical processes and their influence on collagen deposition at the tissue scale.

Annarita Bernardini, Colin Boyle, Arjan Geers, Andrea Malandrino, Andrew Narracott, Sajjad Soleimaniamiri

It has been assumed in previous models that the rate of collagen deposition is proportional to the [...]]]> Place: Xipre Room (173.2), PRBB

Time: 11:00 AM Friday October 8th

Presentations (still preliminar order):

Modification of aneurysm development by chemical processes and their influence
on collagen deposition at the tissue scale.

Annarita Bernardini, Colin Boyle, Arjan Geers, Andrea Malandrino, Andrew Narracott, Sajjad Soleimaniamiri

It has been assumed in previous models that the rate of collagen deposition is proportional to the existing mass of collagen within a developing aneurysm. We will discuss development of such a model to include the influence of chemical factors within the aneurysm tissue.

Endothelial cells affect elastin degradation in aneurysm formation and growth as a function of wall shear stress

Xènia Albà, Claudia M. Amatruda, Iolanda Decorato, Vera Gramigna, Brandis Keller, Jan Marggeta, Giulia di Tomaso

Aberrant values of WSS induce chemical expression of matrix-metalloproteases (MMPs) from the endothelial cells. The MMPs (generally referred to as elastase) degrade the elastin and weaken the mechanical strength of the arterial wall leading to aneurysm formation and growth.

Drug induced effects on the heart: a computational study from molecular to tissue level

Benjamin Bhattacharya-Ghosh, Nils Drechsel, Ana Ferrer Albero, Eduardo Jorge Godoy, Stefano Morotti, Jérome Noailly, Cristian Obiol, Juliusz Stasiewicz

The mechanisms known for drug-induced ion channel blocking suggested that such problem could be computationally approached starting from molecular dynamics to eventually model tissue electrical activity and contractility.

Thus, we present a computational methodology that predicts some effects of drugs on the Ikr current and couple the results on a model of cardiac cell and tissue.

During the week, the different groups will be working in the proposed models for UC2-4. Some speakers are going to be available for questions and discussions during the week. Here is a table of available times.

We will [...]]]>

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During the week, the different groups will be working in the proposed models for UC2-4. Some speakers are going to be available for questions and discussions during the week.
Here is a table of available times.

We will provide the contact details when needed.

Attached is the list of participants and the groups they are participating in

and the rooms assigned to each group during the week

On October 4th, you will be able to follow the conferences on-line through this link.

Open Question:

Title: Sophisticating representation of vascular cells in models of aneurysm evolution:

Overview: There is a general need for more sophisticated models of arterial growth and remodelling which explicitly represent vascular cells, their functionality and their interaction with mechanical stimuli. Such models may yield improved insight into the aetiology of  vascular disesase, [...]]]>

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Open Question:

Title: Sophisticating representation of vascular cells in models of aneurysm evolution:

Overview: There is a general need for more sophisticated models of arterial growth and remodelling which explicitly represent vascular cells, their functionality and their interaction with mechanical stimuli. Such models may yield improved insight into the aetiology of  vascular disesase, e.g. the development of aneurysms.

Task: Develop mathematical model to describe how fibroblast interacts
with its mechanical environment, e.g. relating protein expression (pro-collagen/MMPs)
to cyclic stretch stimuli. Integrate this into a simple model of  aneurysm evolution, e.g. enlarging cylindrical/spherical membrane.

Problem UC3.1:

A major concern for pharmaceutical industry is drug cardiotoxicity, consisting on side effects in the heart that can result in lethal arrhythmias such as Torsades de Pointes. The drugs affect the heart at the ion channel level. However, arrhythmias develop at the whole organ level and therefore the problem of [...]]]>

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Problem UC3.1:

A major concern for pharmaceutical industry is drug cardiotoxicity, consisting on side effects in the heart that can result in lethal arrhythmias such as Torsades de Pointes. The drugs affect the heart at the ion channel level. However, arrhythmias develop at the whole organ level and therefore the problem of drug cardiotoxicity is intrinsically multiscale.

It is still unclear how drug-induced effects at the ion channel level can result in the development and sustenance of cardiac arrhythmias. A multiscale model of drug-induced effects on the heart from ion channel to tissue will be developped to evaluate the role of different currents and intercellular coupling in initiating and modulating pro-arrhythmic events.

Problem UC3.2:

Another important issue in drug development is the fact that certain drugs affect cardiac contractility through directly affecting ionic currents and cardiac dynamics. A multiscale model including coupling of electrophysiology and contraction at the cellular level will be developed to investigate how drug-induced effects in ionic currents can affect calcium dynamics and contractility in isolated cells and tissue.

In both problems, the main tools that could be used are mathematical models of the action potential and contraction available in the cellML repository and COR, Matlab and Chaste as simulation tools.

Problem UC2.1:

We shall present lumped and multimodel descriptions of the lung from the mechanical standpoint. Concerning diffusion of oxygen in the blood, lumped model can also be designed, but they cannot account for  the fact that oxygen in not uniformly distributed over the lung, and that a better efficiency can be obtained [...]]]>

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Problem UC2.1:

We shall present lumped and multimodel descriptions of the lung from the mechanical standpoint.
Concerning diffusion of oxygen in the blood, lumped model can also be designed, but they cannot account for  the fact that oxygen in not uniformly distributed over the lung, and that a better efficiency can be obtained by increasing the breathing frequency.
It calls for multiscale / multimodel  approach of the lung for advection -diffusion aspects also.
Some attempts have been made in this direction, but no general model exists. We shall present some facts, which may constitute the bricks of a future integrated model.

Problem UC2.2:

This second issue is wide open. It concerns the role of the smooth muscle in the respiratory process. This muscle contracts during ventilation, thereby reducing the diameter of branches and increasing the overall resistance, so that it costs more energy to ventilate. The survival advantage of having those muscles in the respiratory tract is not obvious (and still debated), and this questions can be investigated with lumped or more sophisticated models.

Multiscale simulations in biomedicine appears to be an exciting topic for the second study group of the Virtual Physiological Human Network of Excellence. Based on the successful stories of the 1st SG held in Nottingham but also on similar activities carried out in previous netowrks and projects like INFOBIOMED, QosCosGrid or [...]]]>

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Multiscale simulations in biomedicine appears to be an exciting topic for the second study group of the Virtual Physiological Human Network of Excellence. Based on the successful stories of the 1st SG held in Nottingham but also on similar activities carried out in previous netowrks and projects like INFOBIOMED, QosCosGrid or BioBridge, the activity is somwhere in between a workshop and a school, trying to take the most of each of them.

Interactivity is sometimes missing in workshops (despite their name) and work into deep problems is missing in schools, which typically devote to showing some standard ways to approach scientific problems. The SG, instead, aims at bringing researchers to a common problem and making them collectivelly think in possible solutions. Every background is welcome, and the different groups will be made according to criteria as multidisciplinariety.

Everything is ready for the new study group, and I am sure we will have an extraordinary experience doing science for 5 days in Barcelona. Science in the PRBB, a perfect set up.