Welcome

Welcome to the Systems Biology Laboratory at the University of Melbourne.

At the Systems Biology Lab we build and analyse mathematical models of biological processes, pathways and networks, and the cellular geometries within which these processes take place. We apply these models to problems in human health and physiology, including heart disease, cancer, nanomedicine, and in synthetic biology.

We are based in the School of Mathematics and Statistics and in the Department of Biomedical Engineering at the University of Melbourne.

We are also part of the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology.

For more information contact Lab Director Professor Edmund Crampin
edmund.crampin@unimelb.edu.au

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Corrected pair correlation functions for environments with obstacles – published in Physical Review E

Pair correlation is used widely across biology, ecology and physics, as well as in other areas, to obtain estimates of spatial structure. Environments with obstacles or voids that inhibit and alter the motion of individuals within that environment can give rise to spurious spatial correlations. We present a corrected pair correlation function for lattice-based domains that accounts for obstacles contained within the domain, and show that this ‘obstacle pair correlation function’ is necessary for isolating the correlation associated with the behavior of individuals, rather than the structure of the environment.

Congratulations to Stuart on this paper!

S.T. Johnston, E.J. Crampin (2019)
Corrected pair correlation functions for environments with obstacles
Physical Review E 99, 032124

 

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Mathematical modelling indicates that lower activity of the haemostatic system in neonates is primarily due to lower prothrombin concentration – Scientific Reports

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Our new paper “Mathematical modelling indicates that lower activity of the haemostatic system in neonates is primarily due to lower prothrombin concentration” is now published at Scientific Reports.

This is work by Ivo Siekmann which arose from a fantastic collaboration with Paul Monagle and Vera Ignjatovic from the Murdoch Childrens Research Institute.

I Siekmann, S Bjelosevic, K Landman, P Monagle, V Ignjatovic, EJ Crampin (2019)
Mathematical modelling indicates that lower activity of the haemostatic system in neonates is primarily due to lower prothrombin concentration
Scientific Reports 9 (1), 3936

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New Preprint: Modelling the interaction between RyR and IP3R calcium release in cardiomyocytes

hilary Calcium signalling plays a central role in heart cells. With each heart beat, calcium is released from intracellular stores (SR) via RyR channels to trigger contraction. However, calcium signalling is also implicated in controlling the growth of heart cells, as occurs during development, in response to exercise, and in hypertrophic heart disease. This calcium signal triggers gene expression in the nucleus, and occurs via release of calcium through IP3R channels. How these two distinct calcium signals can occur at the same time is not well understood.

Here we present a mathematical model of calcium release through RyRs and IP3Rs which demonstrates that the interaction between these two calcium signalling mechanisms can increase the duty cycle of the cytosolic calcium transient (that is, increase the period during which calcium remains elevated during each cycle). This finding is consistent with recent experiments which showed that an increase in the duration of elevated cytosolic calcium leads to hypertrophy-related gene transcription.

Therefore, our work, together with the recent experimental study, suggests a plausible mechanism for IP3R-dependent hypertrophic signalling by calcium in cardiomyocytes.

This work was conducted by Hilary Hunt, in collaboration with the Soeller (Exeter) and Roderick (Leuven) labs.

H. Hunt, G. Bass, C. Soeller, L. Roderick, V. Rajagopal, E.J. Crampin
How does interaction between RyR and IP3R mediated calcium release shape the calcium transient for hypertrophic signalling in cardiomyocytes?
arXiv:1902.04851

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New Preprint: Development of a 3D computational model of calcium release in heart cells

david-fig.pngOur new preprint on bioRXiv describes the development of a structurally realistic 3D computational model of a cardiomyocyte which we use to simulate reaction-diffusion of calcium release from RyR clusters during the initial phase of the cardiac calcium transient. We use the model to validate a recent algorithm, CaCLEAN, adapted from radio astronomy to detect spatial locations of RyR clusters and their functional response in living cells from imaging data.

This work was conducted by Dr David Ladd, and is a collaboration with the Soeller (Exeter) and Roderick (Leuven) labs.

D. Ladd, A. Tilunaite, C. Soeller, H.L. Roderick, E.J. Crampin, V. Rajagopal
Detecting RyR clusters with CaCLEAN: influence of spatial distribution and structural heterogeneity
bioRXiv:10.1101/549683

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The impact of mitochondrial organisation on heart cell bioenergetics – published in PLoS Computational Biology

Heart cells contain a high volume of mitochondria, which are necessary to generate the ATP energy supply that is needed to sustain normal heart function.

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Previously, mitochondria were understood to be arranged in a regular, crystalline pattern in heart cells which, it was argued, would facilitate a steady supply of ATP under different workloads. In a new paper by Shourya and many colleagues, in a study led by Vijay Rajagopal, new electron microscopy images show that mitochondria are not regularly arranged in cardiomyocytes. A spatially accurate computational model suggests that this heterogeneous distribution of mitochondria can lead to non-uniform energy supply and hence imbalanced contractile force production across the cell under stress conditions such as during heart failure.

The new study, ‘Insights on the impact of mitochondrial organisation on bioenergetics in high-resolution computational models of cardiac cell architecture’, is published in PLoS Computational Biology:

https://doi.org/10.1371/journal.pcbi.1006640

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Matt Faria – best paper award

matt-faria
Congratulations to Matt Faria – winner of a Best Paper award at the CNBS annual meeting for his paper ‘Minimum Information Reporting in Bio–Nano Experimental Literature’ Nature Nanotechnology 13, 777–785 (2018)

http://doi.org/10.1038/s41565-018-0246-4

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New Preprint: Maintaining the stem cell niche in multicellular models of epithelia

Claire Miller’s new preprint is available now on arXiv.

https://arxiv.org/abs/1811.10781

In epithelial tissues such as skin, stem cells divide in order to replace cells that are lost at the surface. The maintenance of the stem cell niche is therefore an important component of any mathematical model of an epithelial tissue. In this paper we investigate how current modelling methods can result in erroneous loss of stem cells from the stem cell niche. Using established models of skin we find we are unable to maintain a stem cell population without including additional unbiological mechanisms. We suggest an alternative modelling methodology to maintain the stem cell niche in which a rotational force is applied to the two daughter cells during the mitotic phase of division to enforce a particular division direction. This methodology reflects the regulation of orientation of the mitotic spindle during the final phase of the cell cycle. We show using an agent-based multicellular model of human skin that this additional, biologically plausible mechanism is sufficient to maintain the stem cell niche.
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