A Multiscale approach to Bone Remodelling
A Joint Project of
Modelling and Simulation Laboratory , University of Camerino
Istituti Ortopedici Rizzoli, Sheffield University
Computer Laboratory, University of Cambridge
Main investigators:
Emanuela Merelli, University of Camerino
Marco Viceconti, Istituti Ortopedici Rizzoli, Sheffield University
Pietro Lio', University of Cambridge
Bone Remodelling Team is exploring a new formal approach for modelling, analysis and prediction of the bone remodelling.
The aim of the project is to define a new computational model that supports, in a uniform way, the multiscale modelling and the behavioural analysis, from tissue mechanics to molecular interaction and back.
The multiscale complexity of Bone Remodelling turns to be wellsuited to exercise different existing modelling approaches, some of them considered natively multiscale, whereas some others simply adapted so as the one under study.
Coupling different levels of description (micro  meso  macro)
is a great challenge, as it is likewise highlighted by the Virtual Physiological Human (VPH) FP7 project, whose main objective is the development of a computational framework and software tools for the multilevel modelling and simulation of the human anatomy
and physiology.
A similar interest is perceived within the academic field of Formal
Methods, where a growing attention for hierarchical and multiscale models is recently registered.
As well as multiscale, a biological system gives evidence that its behaviour, observable at a certain scale of abstraction, is the result of a well organized scenario at a lower level scale, where an adaptive system, consisting of many components interacting for a common goal, makes an effort to maintain the system environment at higher level, in a certain equilibrium. Thus the modelling must to take into account explicit factors like space, shape, motion and relations as perception and affinity to create faithfull models of biological reality and to allow meaningful analysis of the system properties.
Currently, the spectrum of the approaches used in multiscale modelling range over by PDE ODE coupled systems and Complex Automata (CxA), more recently by Spatial P systems (SP) and BioShape.
Except from ODE/PDE models, the selected approaches aim at putting in evidence two complementary characteristics, which lack in the continuumbased approach: the ability to model the topological space of the components interactions and their motion, respectively supported in CxA, in SPs and both in BioShape.
Even if none of the above approaches fully support all the features that characterized a multiscale biological model, BioShape natively designed for this purpose seams to be promising.
In particular, we propose:
 to investigate on the appropriate computational approach suitable to zoomingin and zoomingout a multiscale model moving through different time and space scales.
 to describe, from the behavioural and topological point of view, BMU machine at cellular level  e.g. by automata, statecharts, adaptive agents, BioShape etc.
 to define an appropriate modal logic for specifying the qualitative and quantitative properties of the BR model we are interested to analyse.
Qualitivative analysis, in terms of correct behavior = reachability; free of unwanted behaviors = safety; warrantee of correct behavior for any input = liveness. And quantitative analysis during the model simulation in terms of,
 "how much mineralized bone is destroyed by an Osteoclast (i.e. the cell responsible for bone resorption) and in how much time?"
 "how many cells are created by an Osteoblast (i.e. the cell responsible for bone regeneration) and in how much time?"
 "what is the maximal size an Osteoclast can reach before starting to erode the mineralized bone?"
 "how orientation of involved actors (Osteoblasts & Osteclast) affect resorption/regeneration activities in term of time and energy loss?"
and
 "what is the expected number of BMUs actived in a certain time period?"
 "what is the expected number of Osteoclasts, Osteoblast, Ostocytes etc. present in a BMU at the Resorption, Reversal, Formation and Resting phases?"
 "how much the genetic expression changes respect to the tension of the bone structure?"
 "how much the bone strength depends on the optimization of the topological space at cellular level?"
 to predict the (behavioural) dynamics of a bone tissue
 to analyse the molecules and cells interactions at different scale levels as a basis to study the drugs interferences
 to represent into the model the personalise genetic information (...) towards a personalized model.
 to apply the new knowledge coming from biological methods and techniques back to the theory of formal methods.
Bone Remodelling team:
 CoSy LabUniversity of Camerino
 Diletta Cacciagrano  Models Expressivity
 Rosario Culmone  SAT Solver in Alloy with HPC
 Luca Tesei  BioSHAPE simulator
 Leonardo Vito, Postdoc  Semantic Management of Models and Parametrs
 Federici Buti, PhD Student  BioSHAPE Implementation
 Nicola Paoletti, Phd Student  Hierarchical Spatial Model
 Matteo Rucco, Master Student  Deplyment of POP (from PDE to ODE and back) in CUDA
 Computer Lab  University of Cambridge
 Istituti Ortopedici Rizzoli  Italy
 Fulvia Taddei
 Martino Pani
 PhD student
Infrastructure and sw:
 CoSy LabUniversity of Camerino
 Five GTX260s boards and one C1060, for GPU computing on CUDA architecture. Offered by Nvidia
 Cluster of 32 parallel processes ...
 BioShape: Agentbased spatial simualtor
 Computer Lab  University of Cambridge
 Istituti Ortopedici Rizzoli  Italy
 Cluster of 32 parallel processes ...
Publications:

M.Paoletti, Merelli E., N., Lio' P., : http://www.nettab.org/2011/. In: NETTAB 2011

Lio' P., Merelli E., Paoletti, N.: Multiple verification in computational modeling of bone pathologies. In: CompMod 2011

M.Paoletti, N., Lio' P., Merelli E., Viceconti M.: Osteoporosis: a multiscale modeling viewpoint. In: CSMB 2011

Buti F., Callisto M., Corradini F., Merelli E., Tesei L.:Multiscale Modelling: a Mobile Membrane Approach. In: MecBic 2011

Lio' P., Merelli E., Paoletti, N., Viceconti M.: A combined process algebraic and stochastic approach to Bone Remodelling . In: CS2BIO 2011

Buti F., Cacciagrano D., Corradini F., Merelli E., Tesei L.: A uniform multiscale metamodel of BioShape . In: CS2BIO 2011

Buti F., Cacciagrano D., Corradini F., Merelli E., Pani M., Tesei L.: Bone Remodelling in BioShape . CS2Bio 2010.
 Cacciagrano D., Corradini F., Merelli E., Tesei L.. Multiscale Bone Remodelling with Spatial P Systems . MeCBIC 2010
Posters:
 Emanuela Merelli, Nicola Paoletti, Pietro Lio'. Osteoporosis: a Multiscale Modeling Viewpoint. ICSB 2011: 12th International Conference on Systems Biology
 Emanuela Merelli, Nicola Paoletti, Pietro Lio'. Methodological Bridges for Complex Systems. Awarded at FET11: The European Future Technologies Conference and Exhibition
D.Cacciagrano, F.Corradini, E.Merelli, M.Viceconti. Reasoning on proximal model for multiscale spatial dynamics in Bone Remodelling . VPH Conference 2010
 Federico Buti, Diletta Romana Cacciagrano, Flavio Corradini, Emanuela Merelli and Luca Tesei. Bone Remodelling @ UNICAM . CMSB 2010
 Massimo Callisto De Donato, Flavio Corradini, Maria Rita Di Berardini, Emanuela Merelli and Luca Tesei. Tailoring the Shape Calculus for Quantitative
Analysis. MLQA 2010
Invited Talks:
Research Projects:
Research Meetings:
 29 August 2 September 2011  Cambridge
 15 October 2010  Bologna
 610 September 2011  Cambridge
 28 June 2010  Bologna (report)
 12 March 2010  Camerino article for CS2BIO
 23 February 2010  Skype (report)
 15 January 2010  Bologna (report)
Correspondences:
Opportunities:
You might also like to visit the research opportunities
page.
Nicola Paoletti received the HPC fellowship in 2011 for visiting Edinburgh, and Cambridge
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