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Modelling calcium signalling in in-vitro fertilisation

Sadeghi Namaghi, Layla 2022. Modelling calcium signalling in in-vitro fertilisation. MPhil Thesis, Cardiff University.
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Calcium (Ca2+) signalling plays a crucial, diverse role in the body (Berridge et al., 2003). We focus on the role of Ca2+ signalling in the fertilisation of mammalian eggs (Sanders et al., 2018). Many models of Ca2+ signalling rely on inaccurate dynamics of the inositol 1,4,5-triphosphate receptor (IP3R) on the Endoplasmic Reticulum (ER) (Theodoridou et al., 2013). It is also frequently assumed that Ca2+ oscillations are driven by the emptying of the ER Ca2+ store and not by the IP3R dynamics. Here, we develop a new ‘gating’ model for Ca2+ signalling in fertilisation that more accurately captures the open probability of the IP3R dynamics, as a function of Ca2+ and IP3, as determined by Mak et al. (1998). To develop a detailed understanding of gating models, we first study the models of Atri et al. (1993) and Li and Rinzel (1994). Subsequently, we study Mak et al. (1998), which includes the most up-to-date experimental data on the IP3R dynamics. We also review how these data have been incorporated into a model by Kowalewski et al. (2006), though the latter is not a model for Ca2+ signalling in fertilisation. Our model combines features of the Atri et al. (1993) model with the IP3R data by Mak et al. (1998). It contains one ODE for [Ca2+] in the cytosol and another ODE for the percentage of non inactivated IP3R. We perform linear stability analysis and solve the model numerically, varying [IP3] as the bifurcation parameter. This model accurately reproduces key experimental features, including the low frequency and large amplitude of Ca2+ oscillations in fertilisation. The model also captures that frequency and amplitude of Ca2+ oscillations increase as [IP3] is increased (Sanders et al., 2018). With this model, we hope to guide future experiments that could eventually improve clinical practice in In-Vitro Fertilisation.

Item Type: Thesis (MPhil)
Date Type: Completion
Status: Unpublished
Schools: Mathematics
Date of First Compliant Deposit: 14 October 2022
Last Modified: 14 Oct 2022 09:16

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