Aban Shuaib’s multi-disciplinary research is at the interface between medicine, engineering and computational modelling. He is a part of the MultiSim project work-package 5, which focuses on modelling molecular and cellular events triggered when a cell is exposed to mechanical stimulation, has been working on the simulations of bone remodelling using agent based modelling (ABM) was invited to present his work at McGill University (Montreal, Canada). Aban was invited by Professor Luc Mongeau, Chair of the Department of Mechanical Engineering (https://www.mcgill.ca/mecheng/people/staff/lucmongeau) and Dr Nicole Li-Jessen, Assistant Professor at the School of Communication Sciences and Disorders (https://www.mcgill.ca/scsd/nicole-li-jessen-phd). This was in light of their groups’ ambition to develop a multi-scale computational model for vocal folds damage; the model will integrate the ABM paradigm.
Aban explained, “Developing multi-scale models which integrate ABM is an area I am developing my expertise in the MultiSim project. McGill University is ranked as one of the top research universities in Canada and globally. Dr Li-Jessen’s group have developed computational infrastructure and methodologies, allowing for efficient simulation parallelisation on high performance computers and live model visualisation and data analysis. These techniques are resolving bottleneck issues in ABM research and have the potential to accelerate its impact. Thus, collaboration and knowledge exchange between the groups at the University of Sheffield and McGill University will have mutual benefits. Therefore, part of my visit was to see the infrastructure and the projects underway in Li-Jessen’s and Mongeau’s group.”
“My talk presented the main outputs from work-package 5, which centred on a mechanical-ABM hybrid model, linking tissue, cellular and molecular events. The model examined the dynamic cell-extracellular matrix interaction (mechanoreciprocity) and the resultant intracellular signalling dynamics, specifically at the level of the protein ERK (Extracellular signal-regulated kinases). One immediate outcome of my visit, based on the presentation, was professors Luc’s group interest in examining the dynamics of ERK activation as part of their mechanostimulation regimes. The second outcome was a road map on the writing a future joint grant to develop a computational model for fibrosis. This will be submitted in September 2019 as a Marie Skłodowska-Curie Global Fellowship. This collaboration might also yield a strategic collaboration with industrial partners such as MIMETAS B.V., a biotechnology company developing human organ-on-a-chip tissue models and products for drug development.”
MultiSim researcher, Aban Shuaib, wins a Santander Mobility Award to visit Institute for Bioengineering of Catalonia (IBEC), Barcelona to develop collaborations with the Cellular and Molecular Mechanobiology Laboratory (CMML) based there.
The Santander Mobility Awards are available for University of Sheffield researchers and research students who wish to carry out collaborative research with colleagues from a Santander Universities partner. It is essentially a Knowledge Exchange grant, to establish new collaborations or strengthen existing ones; it is not a project grant.
Aban explains, “During my post at MultiSim, I have developed a novel computational model (CoM) which examining the dynamic interaction between the cell and extracellular environment (ECM). The model shed light on this relationship and connected elements of mechanosensation and mechanotransduction together. Nonetheless, the model requires validation via wet-lab experiments. Therefore, I communicated with several European research groups to explore visits and potential cooperation to co-design and execute validation experiments (short term aim) and, if needed, to collaborate to write a joint grant which will lead to extensive CoM validation (long term aim).
One of these groups was the Cellular and Molecular Mechanobiology Lab (CMML, http://www.ibecbarcelona.eu/cellmolmech) in the Institute for Bioengineering of Catalonia (IBEC). Consequently, I have applied for the Santander Mobility Awards to visit CMML group for three weeks to initiate and establish these links, in addition to plan future experiments with the group members. I was fortunate to have been awarded this grant to build bridges with the group. During the visit, I interacted with lab members over experimental set-ups and designs, some of these are providing the spine for experiments and measures in a research proposal I am writing with the CMML group leader (Pere Roca-Cusachs Souler) and collaborators at McGill University (http://multisim-insigneo.org/multisim-researcher-aban-shuaib-invited-to-mcgill-university-canada-to-present-his-agent-based-modelling-abm-work/). The Santander Mobility Awards will allow me to host a reciprocal visit by a member of CMML.”
Researchers from our MultiSim project have published a paper in the journal PLoS One on ‘Prenatal growth map of the mouse knee joint by means of deformable registration technique’.
Joint morphogenesis is the process of development of the joint that starts before the birth.
It is important to study joint morphogenesis in order to understand how it is related to musculoskeletal diseases and to optimise related interventions. In several cases the interventions are tested on animal models and the mouse pre-natal model is typically used to test the effect of diseases and treatments on the joints.
In this study, we developed a procedure that combines Optical Projection Tomography imaging (OPT) and a deformable registration algorithm to obtain realistic 3D realistic high-resolution developmental map of the prenatal mouse knee joint. We have found that the developed procedure has acceptable uncertainties of the displacement measurements and that it is well reproducible.
This approach will be used to study how growth and adaptation are directed by biological and mechanobiological factors.
Giorgi, M., Sotirou, V., Franchini, N., Conigliaro, S., Biganardi, C., Nowlan, N. C., Dall’Ara, E., (2019), “Prenatal growth map of the mouse knee joint by means of deformable registration technique”, PLoS One, 14 (1): e0197947, URL: https://doi.org/10.1371/journal.pone.0197947
Graphical Abstract, showing cells, atomic force microscopy and the effect of sample size on the coefficient of variance of the Young’s modulus of the cells
Researchers from our MultiSim project have published a paper in the Journal of the Mechanical Behavior of Biomedical Materials on the ‘Effect of cell sample size in atomic force microscopy nanoindentation’.
Cells in the human body can be classified in many different ways. One of these is looking at their mechanical properties, and therefore at how stiff or soft they are. This characteristic has been shown to correlate to different functions in health and disease, with cells changing their mechanics when undergoing specific processes. A method to characterise cell mechanics is atomic force microscopy: a probe is pressed on the sample and an indentation at the nano-scale is performed.
Cell populations, however, present a certain degree of variability in their characteristics and therefore a suitable number of cells have to be tested to obtain reliable information on their mechanics. The aim of this work is to propose a tool to get this estimate. To achieve this, a large dataset of indentation measurements was obtained on bone cells and analysed to study population variability. The developed tool is made available as an open-source repository and guidelines are provided for its use for atomic force microscopy experimental design:
Insigneo researchers (from left to right) Dr Bryant Roberts, Mr Liam Boyle, Dr Enrico Dall’Ara, Dr Vee San Cheong and Dr Dharshini Sreenivasan
From 2 – 5 April 2019 a team of Insigneo researchers, comprised of Dr Bryant Roberts, Dr Vee San Cheong, Dr Dharshini Sreenivasan, Mr Liam Boyle and led by MultiSim researcher Dr Enrico Dall’Ara, attended the Diamond Light Source I13 X-ray Imaging Lab in the Harwell Science and Innovation Campus, Oxfordshire. Here the team acquired 3D images of the mouse tibia cortical and trabecular bone using pink light, which at the I13 beamline has flux over a million times higher than that of a laboratory X-ray source. This enabled the very rapid imaging of our specimens at higher resolution (with 1.6 µm voxel size) and with higher signal to noise ratio than is achievable with desktop micro-computed tomography (microCT).
The data generated will be used to investigate the effects of pharmacological treatment and mechanical stimuli on the mouse bone tissue. This includes studying the individual and combined effects of bone anabolic treatments, including parathyroid hormone and mechanical loading, in a mouse model with oestrogen-deficiency related bone loss. This research will extend findings from two recent longitudinal microCT imaging studies within MultiSim to examine variations in the osteocyte lacunae distribution and vascular canal morphology; nanostructures that could not be resolved using standard Desktop microCT systems in reasonable time.
Dr Bryant Roberts commented : “The opportunity to contribute in the formulation and writing of a research proposal for the Diamond Light Beamtime was an invaluable experience in my growth as an early career researcher. I look forward in future to realising the exciting outputs from this work as we reveal new insights into treatment effects at the different dimensional scales of bone.”
Beamtime on the Diamond Manchester Imaging Beamline (I13-2) was awarded to Dr Enrico Dall’Ara and Dr Bryant Roberts for proposal No: MG21628 “Assessing the individual and combined effects of parathyroid hormone (1-34) and mechanical loading on the micro- and nano-structural properties of murine cortical bone”. This study was partially funded by EPSRC MultiSim Grant: EP/K03877X/1, UK National Centre for Replacement, Refinement and Reduction of Animals in Research Grant: NC/R001073/1 and by Diamond Light Source.