2 PhD positions to advance integrated computational simulations of intervertebral disc degeneration

Lower back pain (LBP) is the largest cause of morbidity worldwide, yet there remains controversy as to the specific cause leading to poor treatment options and prognosis. Intervertebral disc degeneration (LDD) is reported to account for 50% of LBP in young adults, but the interplay of factors such as genetics, environmental, cellular responses, social and psychological is poorly understood. Unfortunately, the integration of such data into a holistic and rational map of degenerative processes and risk factors has not been achieved, requiring the creation of professional cross-competencies, which current training programmes in biomedicine, biomedical engineering and translational medicine fail to address, individually.

Disc4All aims to tackle this issue through collaborative expertise of clinicians; computational physicists and biologists; geneticists; computer scientists; cell and molecular biologists; microbiologists; bioinformaticians; and industrial partners. It provides interdisciplinary training in data curation and integration; experimental and theoretical/computational modelling; computer algorithm development; tool generation; and model and simulation platforms to transparently integrate primary data for enhanced clinical interpretations through models and simulations. Complementary training is offered in dissemination; project management; responsible research and innovation; ethics; regulation; policy; business strategy; public and patient engagement. Disc4All will train a new generation of internationally mobile professionals with unique skill sets for the development of thriving careers in translational research applied to multifactorial disorders.

Position 1:

Topic: Multiscale modelling of IVD cell activity & potential tissue turnover

Description: The successful candidate will work on the multiscale modelling of the mechanisms of intervertebral disc regulation. Specifically, the work will target the modelling and simulation of bottomup processes of tissue regulation, through which the dynamics of cell activity contributes to disc tissue turnover in specific regions of interest, in response to multifactorial cell stimulations. Different types of intervertebral disc network models will be used and combined to successively incorporate cell culture experimental data, proteomics measurements and eventually gene variant effects. Interplays of biochemical, mechanical and nutritional cell stimulation will be modelled in representative volume elements through agent-based modelling. Eventually, collective cell activity will be linked with heterogeneous cell environments predictable through finite element simulations of disc tissue and organ multiphysics.

Supervision: Jérôme Noailly (UPF)

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Position 2:

Topic: Bottom-up simulations of spatio-temporal degenerative events in the IVD & biological LDD stratification

Description: The successful candidate will work on the systematization of multiscale modelling of the intervertebral disc regulation for improved LDD stratification. Existing regulatory network and multiphysics models, at the molecular/cell and tissue/organ scales will be locally integrated in relevant regions of interest of the IVD. Such integration will be coupled with different disc model morphologies and molecular signature inputs, from the Twins UK and Northern Finland Birth cohorts. A smart atlas of simulated data will be generated, to eventually enable efficient calculations through metamodeling. Metamodeling will further allow the mining of simulated and real word data altogether, to establish different fingerprints of LDD and the spatio-temporal evolution thereof, characterised by specific hierarchies of risk factors and exploitable clinically.

Supervision: Jérôme Noailly (UPF)

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