Control-based Continuation of Solutions and Bifurcations in Dynamic-Clamp-Constructed Hybrid Bursting Systems
Lead Research Organisation:
University of Bristol
Department Name: Engineering Mathematics and Technology
Abstract
Control theory is an interdisciplinary branch of engineering and mathematics that deals with the behaviour of dynamical systems. It is built up around a few very simple ideas, such as feedback loop and stability. Control theory concerns itself with means by which to alter the desired output of a system, called the reference. When one or more output variables of a system need to follow a certain reference over time, a controller manipulates the inputs to a system to obtain the desired effect on the output of the system. Systems can usefully be defined in almost any discipline - they are not confined to engineering or mathematics. The idea behind this proposal is to develop novel control techniques applicable to real biological cells. In particular, we are interested in the behaviour of excitable cells, described mathematically by nonlinear dynamical systems.Excitability of cells and tissues is a basic function of life. It is the ability of cells to respond to stimuli. Excitability is necessary for the functioning of nerves, muscles, and hormones, among other things. The basis for the excitability of cells is their ion distribution, and the distribution of ions and molecules is determined by transport mechanisms associated with their plasma membrane structure. This structure permits and regulates various forms of ionic and molecular transport. The ability of experimentalists to perturb biological systems has traditionally been limited to rigid pre-programmed protocols or more flexible, but reflex constrained, operator-controlled protocols. In contrast, real-time control allows the researcher to dynamically probe a biological system with parameter perturbations that are calculated functions of instantaneous system measurements, thereby providing the ability to address diverse unanswered questions that are not amenable to traditional approaches.There is a great deal of experimental data on one hand and a wealth of theoretical knowledge about excitable systems on the other. This project aims to bridge the gap between theory and experiments by exploring and designing novel techniques for investigation and control of excitable cell systems in real experimental settings. In a long term, such a technology will open completely new avenues for research in development of effective therapies for diseases associated with excitable cell dysfunction.
Planned Impact
As well as the specific academic beneficiaries listed in the Academic Beneficiaries section, the public and a wider academic community will benefit from the increase in knowledge about basic excitable cell physiology and thus brain, heart and muscles function as well as regulation of hormonal secretion. This project also has a great scope towards the medical community, clinical neuroscience and public health. Sectors of the pharmaceutical industry working to develop effective drug therapies for diseases based on excitable cell disorders will also benefit from the proposed work. Indirectly, and in the long term, people suffering from such diseases may also benefit. Therefore, there is the potential for beneficial impact on both the health and wealth of the UK. The ability of an excitable cell to generate a response (in the form of action potential spike or burst) is an important guide to its health. Research into numerous diseases such as neurological disorders, high blood pressure, angina, abnormal heart rhythms, diabetes, etc. has found deficits in ion channels function and specifically the ability to correctly respond to stimuli. This has led to the current idea that these diseases may be classed as channelopathies . Therefore, the mechanisms that we will study in our research will be incorporated into the body of knowledge about these debilitating diseases, for example, informing the development of animal models of disease, which amongst other things, pharmaceutical companies extensively utilise as part of the drug development process. The social impact and economic costs of the diseases mentioned above are enormous. Therefore our work will benefit society from the advances we make in investigating mechanisms that may underlie such diseases, and will benefit the economy both in terms of costs saved in care for patients suffering from these conditions, and also in profits from pharmaceuticals developed and sold by UK-based companies. We acknowledge that these indirect benefits may take several years before they are realised. Following my recent appointment at the University of Bristol as a Lecturer in Engineering Mathematics, the impact of this award on my prospects, as an independent researcher, will be large as it will allow me to start up my intended research programme. The proposed study is highly ambitious, and will draw on the experience of leading researchers at the University of Bristol. It will use interdisciplinary approaches, such as mathematical modelling, computer programming and iterative cycles with wet-lab experiments to validate the models and test model predictions. I have personally developed and analysed the models to be used in this study, and this project will allow me to gain further knowledge and develop a number of new skills. Due to its unprecedented character this project will most likely lead to a number of high impact publications to be generated in the course of the work.
Publications
Slowinski P
(2016)
Dynamic similarity promotes interpersonal coordination in joint action.
in Journal of the Royal Society, Interface
Slowinski P
(2016)
Effects of time-delay in a model of intra- and inter-personal motor coordination
in The European Physical Journal Special Topics
Slowinski P
(2014)
Kinematic characteristics of motion in the mirror game
Slowinski P
(2017)
Unravelling socio-motor biomarkers in schizophrenia.
in NPJ schizophrenia
Slowinski P
(2020)
Neurologically Motivated Coupling Functions in Models of Motor Coordination.
in SIAM journal on applied dynamical systems
Smith P
(2018)
A Drosophila Model of Essential Tremor.
in Scientific reports
Smith P
(2019)
Shaw and Shal voltage-gated potassium channels mediate circadian changes in Drosophila clock neuron excitability.
in The Journal of physiology
Szalai R
(2011)
Nonlinear models of development, amplification and compression in the mammalian cochlea.
in Philosophical transactions. Series A, Mathematical, physical, and engineering sciences
Teka W
(2011)
From plateau to pseudo-plateau bursting: making the transition.
in Bulletin of mathematical biology
Tigaret CM
(2013)
Wavelet transform-based de-noising for two-photon imaging of synaptic Ca2+ transients.
in Biophysical journal
Description | The research funded on EP/I018638/1 grant has contributed to our understanding of how to design and analyse hybrid systems interfacing a living system (such as biological cell, organ, tissue, or a human being) with computer program implementing mathematical formulation of an important dynamic component of the living system under investigation. |
Exploitation Route | Some of the ideas developed as part of EP/I018638/1 have been now used in one of my current research grants: 01/02/2013 - 31/01/2016 (PI - Exeter) EU FP7 ICT 2.9 - Cognitive Sciences and robotics (€2,900,000) collaborative project, Title: AlterEgo: Enhancing social interactions using information technology, coordinated by Prof Benoît Bardy at Montpellier 1 University in France. The project also involves computer science experts from the DFKI centre (Germany), roboticists from the Ecole Polytechnique Fédérale de Lausanne (CH), as well as clinicians, psychologists and psychiatrists from the Academic Hospital of Montpellier (CHRU, FR). |
Sectors | Digital/Communication/Information Technologies (including Software) Healthcare Pharmaceuticals and Medical Biotechnology |
Description | EPSRC Centres for Mathematical Sciences in Healthcare |
Amount | £2,008,955 (GBP) |
Funding ID | EP/N014391/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2016 |
End | 12/2019 |
Description | EPSRC Impact Acceleration Account (IAA) Impact and Knowledge Exchange Award |
Amount | £65,942 (GBP) |
Funding ID | Pfact ID: 9372 |
Organisation | University of Exeter |
Sector | Academic/University |
Country | United Kingdom |
Start | 03/2018 |
End | 09/2018 |
Description | EU FP7 |
Amount | € 2,900,000 (EUR) |
Funding ID | 600610 |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start | 02/2013 |
End | 01/2016 |
Description | AlterEgo: Enhancing social interactions using information technology |
Organisation | University of Montpellier |
Country | France |
Sector | Academic/University |
PI Contribution | Partner on the EU grant |
Collaborator Contribution | Coordinating the EU grant |
Impact | Collaborative project, Title: AlterEgo: Enhancing social interactions using information technology, coordinated by Prof Beno?t Bardy at Montpellier 1 University in France. The project also involves computer science experts from the DFKI centre (Germany), roboticists from the Ecole Polytechnique F?d?rale de Lausanne (CH), as well as clinicians, psychologists and psychiatrists from the Academic Hospital of Montpellier (CHRU, FR). |
Start Year | 2011 |
Description | Engagement with Avon and Wiltshire Mental Health Partnership NHS Trust and Devon Partnership NHS Trust |
Organisation | Avon and Wiltshire Mental Health Partnership NHS Trust |
Country | United Kingdom |
Sector | Public |
PI Contribution | We are contributing novel methodology that could potentially help the South West NHS Mental Health Trusts with early diagnosis of psychosis. This is based on real-time human virtual partner interaction and inspired by ideas developed as part of the EPSRC funding I an reporting on. |
Collaborator Contribution | The Avon and Wiltshire Mental Health Partnership NHS Trust and Devon Partnership NHS Trust are contributing access to their Early Intervention Teams, in-kind funding support and expertise. |
Impact | We have secured funding to perform a pilot study involving both, Avon and Wiltshire Mental Health Partnership NHS Trust and Devon Partnership NHS Trust. The collaboration is multidisciplinary and involves, mathematicians, clinical psychologists and psychiatrists. |
Start Year | 2017 |
Description | Engagement with Avon and Wiltshire Mental Health Partnership NHS Trust and Devon Partnership NHS Trust |
Organisation | Devon Partnership NHS Trust |
Country | United Kingdom |
Sector | Public |
PI Contribution | We are contributing novel methodology that could potentially help the South West NHS Mental Health Trusts with early diagnosis of psychosis. This is based on real-time human virtual partner interaction and inspired by ideas developed as part of the EPSRC funding I an reporting on. |
Collaborator Contribution | The Avon and Wiltshire Mental Health Partnership NHS Trust and Devon Partnership NHS Trust are contributing access to their Early Intervention Teams, in-kind funding support and expertise. |
Impact | We have secured funding to perform a pilot study involving both, Avon and Wiltshire Mental Health Partnership NHS Trust and Devon Partnership NHS Trust. The collaboration is multidisciplinary and involves, mathematicians, clinical psychologists and psychiatrists. |
Start Year | 2017 |
Description | Brain Awareness Week, public talk on 15th March 2018 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Undergraduate students |
Results and Impact | The Brain Awareness Week is a global campaign which aims to increase the public's awareness of current brain research. It is taking place from the 12 - 18 March 2018 and the University of Exeter has been awarded funding from the British Neuroscience Association to host a range of workshops and events on brain-related topics. One of our public events is called "Neuroscience: Is it all in our minds?", which is a seminar series introducing a diverse audience to a range of neuroscience ideology and research findings, with an opportunity for questions and networking. |
Year(s) Of Engagement Activity | 2018 |
Description | Interview for the Euro News channel feature |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | During the final workshop for the FP7 funded EU project "AlterEgo", the Euronews channel filmed this interview. |
Year(s) Of Engagement Activity | 2016 |
URL | http://www.euronews.com/2016/10/31/avatars-help-schizophrenia-patients-silence-tormenting-voices |
Description | Real-time dynamic sub-structured testing and control of living systems |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | Yes |
Geographic Reach | National |
Primary Audience | Policymakers/politicians |
Results and Impact | Popularising my research amongst general public Discussions |
Year(s) Of Engagement Activity | 2011 |
Description | Soapbox Science Speaker on the 14th of June 2014 in Bristol |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | This activity was a joined effort with the Bristol Festival of Nature that transformed the city's open spaces into a hub of scientific learning and discussion, as some of the UK's leading female scientists took to their soapboxes to showcase science to the general public. The event's mission remains the same: to help eliminate gender inequality in science by raising the profile, and challenging the public's view, of women and science (http://soapboxscience.org/?page_id=823) |
Year(s) Of Engagement Activity | 2014 |
URL | http://soapboxscience.org/?p=1149 |