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Review: Modelling placental amino acid transfer - From transporters to placental function

Review: Modelling placental amino acid transfer - From transporters to placental function
Review: Modelling placental amino acid transfer - From transporters to placental function
Amino acid transfer to the fetus is dependent on several different factors. While these factors can be understood in isolation, it is still not possible to predict the function of the system as a whole. In order to do this an integrated approach is required which incorporates the interactions between the different determinants of amino acid transfer. Computational modelling of amino acid transfer in the term human placenta provides a mechanism by which this integrated approach can be delivered. Such a model would be invaluable for understanding amino acid transfer in both normal and pathological pregnancies.

In order to develop a computational model it is necessary to determine all the biological factors which are important contributors to net amino acid transfer and the ways in which they interact. For instance, how different classes of amino acid transporter must interact to transfer amino acids across the placenta. Mathematically, the kinetics of each type of transporter can be represented by separate equations that describe their transfer rate as a non-linear function of amino acid concentrations. These equations can then be combined in the model to predict the overall system behaviour. Testing these predictions experimentally will demonstrate the strengths and weaknesses of the model, which can then be refined with increasing complexity and retested in an iterative fashion.

In this way we hope to develop a functional computational model which will allow exploration of the factors that determine amino acid transfer across the placenta. This model may also allow the development of strategies to optimise placental transfer in pathologies associated with impaired amino acid transfer such as fetal growth restriction
placenta, amino acid, epithelial transport, systems biology, computational modelling
0143-4004
S46-S51
Lewis, R.M.
caaeb97d-ea69-4f7b-8adb-5fa25e2d3502
Brooks, S.
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Crocker, I.P.
b8686961-d199-4a28-bd16-bbf71821bd96
Glazier, J.
cd25b20a-e5b6-4697-89cc-6ee8930b8e6d
Hanson, M.A.
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Johnstone, E.D.
354bf081-807b-4ca9-8956-7be1287f834c
Panitchob, N.
93e762fd-2975-49a1-bf64-7a3524e8758d
Please, C.P.
48277c2e-c9eb-46f8-8995-1cf885922818
Sibley, C.P.
6e4ffcd0-f4b5-41c4-8360-9d78b9e9156c
Widdows, K.L.
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Sengers, B.G.
79bf09ff-468d-48f0-992c-828200db8b1f
Lewis, R.M.
caaeb97d-ea69-4f7b-8adb-5fa25e2d3502
Brooks, S.
4b0ecd34-a592-46b3-a21f-f83bdda46c7b
Crocker, I.P.
b8686961-d199-4a28-bd16-bbf71821bd96
Glazier, J.
cd25b20a-e5b6-4697-89cc-6ee8930b8e6d
Hanson, M.A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Johnstone, E.D.
354bf081-807b-4ca9-8956-7be1287f834c
Panitchob, N.
93e762fd-2975-49a1-bf64-7a3524e8758d
Please, C.P.
48277c2e-c9eb-46f8-8995-1cf885922818
Sibley, C.P.
6e4ffcd0-f4b5-41c4-8360-9d78b9e9156c
Widdows, K.L.
25faab47-b4fc-4837-99fb-fa6b0e15398e
Sengers, B.G.
79bf09ff-468d-48f0-992c-828200db8b1f

Lewis, R.M., Brooks, S., Crocker, I.P., Glazier, J., Hanson, M.A., Johnstone, E.D., Panitchob, N., Please, C.P., Sibley, C.P., Widdows, K.L. and Sengers, B.G. (2013) Review: Modelling placental amino acid transfer - From transporters to placental function. Placenta, 34 (Supplement), S46-S51. (doi:10.1016/j.placenta.2012.10.010).

Record type: Review

Abstract

Amino acid transfer to the fetus is dependent on several different factors. While these factors can be understood in isolation, it is still not possible to predict the function of the system as a whole. In order to do this an integrated approach is required which incorporates the interactions between the different determinants of amino acid transfer. Computational modelling of amino acid transfer in the term human placenta provides a mechanism by which this integrated approach can be delivered. Such a model would be invaluable for understanding amino acid transfer in both normal and pathological pregnancies.

In order to develop a computational model it is necessary to determine all the biological factors which are important contributors to net amino acid transfer and the ways in which they interact. For instance, how different classes of amino acid transporter must interact to transfer amino acids across the placenta. Mathematically, the kinetics of each type of transporter can be represented by separate equations that describe their transfer rate as a non-linear function of amino acid concentrations. These equations can then be combined in the model to predict the overall system behaviour. Testing these predictions experimentally will demonstrate the strengths and weaknesses of the model, which can then be refined with increasing complexity and retested in an iterative fashion.

In this way we hope to develop a functional computational model which will allow exploration of the factors that determine amino acid transfer across the placenta. This model may also allow the development of strategies to optimise placental transfer in pathologies associated with impaired amino acid transfer such as fetal growth restriction

Other
1-s2.0-S0143400412004031-main.pdf__tid=a761b294-1640-11e4-ad9a-00000aacb360&acdnat=1406542947_d0247853b554ba51bf9a243d59b5c8b4 - Version of Record
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Published date: March 2013
Keywords: placenta, amino acid, epithelial transport, systems biology, computational modelling
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 367299
URI: http://eprints.soton.ac.uk/id/eprint/367299
ISSN: 0143-4004
PURE UUID: aba4e0dc-ce76-4696-aa50-f594d666bb7d
ORCID for R.M. Lewis: ORCID iD orcid.org/0000-0003-4044-9104
ORCID for M.A. Hanson: ORCID iD orcid.org/0000-0002-6907-613X

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Date deposited: 28 Jul 2014 10:26
Last modified: 18 Feb 2021 16:57

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Contributors

Author: R.M. Lewis ORCID iD
Author: S. Brooks
Author: I.P. Crocker
Author: J. Glazier
Author: M.A. Hanson ORCID iD
Author: E.D. Johnstone
Author: N. Panitchob
Author: C.P. Please
Author: C.P. Sibley
Author: K.L. Widdows
Author: B.G. Sengers

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