Mathematical Modelling of the Chemotherapeutic Drug Paclitaxel
Lead Research Organisation:
University of Dundee
Department Name: Mathematics
Abstract
Paclitaxel (taxol) is front line chemotherapeutic that inhibits cell proliferation by inhibiting mitosis. Despite intense efforts by the research community to identify chemically similar compounds with fewer harmful side effects, progress has thus far been limited.
Adrian Saurin's (co-supervisor, Ninewells) lab has performed series of experiments measuring the uptake and transport of the Paclitaxel (taxol) in a variety of different experimental situations (e.g. cell lines and tumour spheroids). Isaac's project is focussed on using the experimental data to develop and validate mathematical models of transport and uptake of Paclitaxel in different situations. The model will then be adapted so as to describe drug uptake in tumour spheroids and, ultimately, in in vivo contexts.
Ultimately, the aim of the project is to better understand the mechanisms of taxol transport and uptake and to use this information to develop novel strategies for improving taxol treatment protocols.
Objectives:
(1) Use mathematical model to better understand taxol uptake and transport.
(2) Use mathematical models to explain puzzling aspects of the experimental data in a single theoretical framework.
(3) Identify model parameters using bespoke optimisation algorithms.
(5) Use mathematical models to explore different modes of therapy delivery.
Methodology
(1) Derive a novel system of nonlinear ordinary differential equations that describe relevant biological processes.
(2) Derive a novel system of nonlinear reaction diffusion equations that describe spatial transport of taxol in different experimental contexts.
(3) Estimate model parameters using bespoke algorithms that minimising error between experimental data and model solutions.
(4) Use the fitted models to make testable experimental predictions that will lead to novel experiments and treatment strategies.
Adrian Saurin's (co-supervisor, Ninewells) lab has performed series of experiments measuring the uptake and transport of the Paclitaxel (taxol) in a variety of different experimental situations (e.g. cell lines and tumour spheroids). Isaac's project is focussed on using the experimental data to develop and validate mathematical models of transport and uptake of Paclitaxel in different situations. The model will then be adapted so as to describe drug uptake in tumour spheroids and, ultimately, in in vivo contexts.
Ultimately, the aim of the project is to better understand the mechanisms of taxol transport and uptake and to use this information to develop novel strategies for improving taxol treatment protocols.
Objectives:
(1) Use mathematical model to better understand taxol uptake and transport.
(2) Use mathematical models to explain puzzling aspects of the experimental data in a single theoretical framework.
(3) Identify model parameters using bespoke optimisation algorithms.
(5) Use mathematical models to explore different modes of therapy delivery.
Methodology
(1) Derive a novel system of nonlinear ordinary differential equations that describe relevant biological processes.
(2) Derive a novel system of nonlinear reaction diffusion equations that describe spatial transport of taxol in different experimental contexts.
(3) Estimate model parameters using bespoke algorithms that minimising error between experimental data and model solutions.
(4) Use the fitted models to make testable experimental predictions that will lead to novel experiments and treatment strategies.
Organisations
People |
ORCID iD |
Philip Murray (Primary Supervisor) | |
Isaac Proudfoot (Student) |
Publications
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
EP/N509632/1 | 01/10/2016 | 30/09/2021 | |||
2009795 | Studentship | EP/N509632/1 | 01/10/2017 | 31/03/2021 | Isaac Proudfoot |
Description | A mathematical model that quantifies the uptake and retention of the drug paclitaxel by cells and tissue. This model has been fitted to experimental data provided by collaborators at Ninewells Hospital. |
Exploitation Route | Optimising current treatment protocols with the drug and adapting the model to suit different tumour environments. |
Sectors | Pharmaceuticals and Medical Biotechnology |
Title | Mathematical model for paclitaxel in monolayer cultures |
Description | A mathematical model that describes the rate of transport of paclitaxel across the cell membrane and its various binding affinities. |
Type Of Material | Model of mechanisms or symptoms - in vitro |
Year Produced | 2019 |
Provided To Others? | Yes |
Impact | Some hypotheses regarding how paclitaxel is taken up and retained by tissue have been tested and supported by this tool. |
Description | Quantitative Systems Pharmacology Workshop |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Schools |
Results and Impact | A 2 day workshop discussing the various roles for mechanistic and AI driven models in solving problems in pharmacology. |
Year(s) Of Engagement Activity | 2019 |