Regulatory mechanisms in biological systems in response to compound environmental changes
Lead Research Organisation:
Imperial College London
Department Name: Bioengineering
Abstract
All actions in biological systems are controlled by extensive regulatory networks within and across different levels, such as cellular, physiological, and individual levels. In this sense, control is the manifestation of any life activity, and its revelation is the key to understanding the mystery of life . Here, control is considered to be a physical-components-based mechanism used by biological organisms to attain their objectives. The ultimate aim of the proposed research is to establish a theory for biological control, to (re)capture the various phenomena in biological systems from the viewpoint of control, and to reveal the design principles that are common to biological control systems across different levels and different species.Although control has been an essential theme in the field of life sciences for a long time, research on control in life sciences has been developed independently at different levels: homeostasis at the physiological level, cybernetics at the species level, and regulatory biology and more recently systems biology at the cellular level. However, the fact that complex biological regulatory mechanisms have developed through evolution from primitive single-cell organisms with strictly constrained cellular resources suggests that the essential components of regulatory mechanisms might have common features across different levels. I believe that it is thus natural to search for a unified theory of biological control that can provide a viewpoint that will improve our essential understanding of biological regulations in the new era of life sciences. Such a theory is not only crucial in academia but also necessary for accurate assessment and effective treatment of dynamically changing disease states. It should provide essential information for practical clinical treatment towards next-generation healthcare.One of the salient features of biological control systems, compared to man-made ones, is their ability to change their structures and/or functions to match the situation. This plasticity enables biological organisms to adapt to almost any environmental change and to take appropriate actions. Plasticity appears, depending on the time scale, as evolution, differentiation, or learning. Whereas man-made systems use specific regulatory mechanisms corresponding to the environmental change, biological systems, with their limited resources, have to exhibit a broad range of flexible actions with one regulatory mechanism in response to a wide variety of environmental changes. The proposed research focuses on this characteristic and aims to reveal the essential elements of biological control across different levels that attain such plasticity by developing a mathematical theory that can explain the underlying mechanisms of biological control. In particular, I will pursue the underlying regulatory mechanisms from the viewpoint of compound control, the basic idea of which is that complex biological regulations result from spatial and temporal combinations of simple homogeneous computational media, such as interactions among different molecules for cellular control and neuron firings for cerebral control, corresponding to various compound environmental changes. I will focus on the development of a theoretical basis for biological control at the cellular level first and then that in immune systems, which use both cellular- and physiological-level controls. The basic studies at the cellular level on genetic and metabolic systems, together with applied studies on immune systems, both based on the idea of compound control, should reveal the essential design principles of biological control systems.
People |
ORCID iD |
Reiko Tanaka (Principal Investigator) |
Publications
Tanaka G
(2018)
Bifurcation analysis of a mathematical model of atopic dermatitis to determine patient-specific effects of treatments on dynamic phenotypes.
in Journal of theoretical biology
Ejaz N
(2012)
Biomimetic and Biohybrid Systems
Ejaz N
(2013)
Closed-loop response properties of a visual interneuron involved in fly optomotor control.
in Frontiers in neural circuits
Christodoulides P
(2017)
Computational design of treatment strategies for proactive therapy on atopic dermatitis using optimal control theory.
in Philosophical transactions. Series A, Mathematical, physical, and engineering sciences
Ono M
(2016)
Controversies concerning thymus-derived regulatory T cells: fundamental issues and a new perspective.
in Immunology and cell biology
Granados AA
(2017)
Distributing tasks via multiple input pathways increases cellular survival in stress.
in eLife
Eyerich K
(2019)
Human and computational models of atopic dermatitis: A review and perspectives by an expert panel of the International Eczema Council.
in The Journal of allergy and clinical immunology
Miyano T
(2021)
Identification of keratinocyte subpopulations in transcriptome to evaluate drug effects in atopic dermatitis.
in The British journal of dermatology
Tanaka RJ
(2015)
In silico modeling of spore inhalation reveals fungal persistence following low dose exposure.
in Scientific reports
Schwyn D
(2011)
Interplay between Feedback and Feedforward Control in Fly Gaze Stabilization
in IFAC Proceedings Volumes
Domínguez-Hüttinger E
(2017)
Mathematical modeling of atopic dermatitis reveals "double-switch" mechanisms underlying 4 common disease phenotypes.
in The Journal of allergy and clinical immunology
Domínguez-Hüttinger E
(2017)
Mathematical Modeling of Streptococcus pneumoniae Colonization, Invasive Infection and Treatment.
in Frontiers in physiology
Nousbeck J
(2021)
MicroRNA analysis of childhood atopic dermatitis reveals a role for miR-451a.
in The British journal of dermatology
Hurault G
(2020)
Personalized prediction of daily eczema severity scores using a mechanistic machine learning model.
in Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
Van Logtestijn MD
(2015)
Resistance to water diffusion in the stratum corneum is depth-dependent.
in PloS one
Domínguez-Hüttinger E
(2013)
Risk factor-dependent dynamics of atopic dermatitis: modelling multi-scale regulation of epithelium homeostasis.
in Interface focus
Tanaka RJ
(2011)
Skin barrier homeostasis in atopic dermatitis: feedback regulation of kallikrein activity.
in PloS one
Tanaka RJ
(2013)
Skin disease modeling from a mathematical perspective.
in The Journal of investigative dermatology
Jurakic Toncic R
(2021)
Stratum corneum markers of innate and T helper cell-related immunity and their relation to the disease severity in Croatian patients with atopic dermatitis.
in Journal of the European Academy of Dermatology and Venereology : JEADV
Lee SY
(2016)
Synergistic Activation of RD29A Via Integration of Salinity Stress and Abscisic Acid in Arabidopsis thaliana.
in Plant & cell physiology
Ono M
(2014)
Visualisation of the T cell differentiation programme by Canonical Correspondence Analysis of transcriptomes.
in BMC genomics
Van Logtestijn MD
(2016)
Water resistance profile as a marker of skin barrier damage in atopic dermatitis patients.
in Journal of dermatological science
Description | We developed mathematical models and framework to understand the mechanisms of different inflammatory and infectious disease, including atopic dermatitis, fungal infection and bacterial infection. |
Exploitation Route | Our in silico modelling approach opened up a new area of systems dermatology and developed the fungal research. We are developing GUI to suggest optimal treatment strategies for atopic dermatitis, based on our mathematical models. |
Sectors | Healthcare |
URL | http://www.bg.ic.ac.uk/research/r.tanaka/index.html#ourresearch |
Description | Our findings advanced in understanding disease mechanisms (eczema, fungal and bacterial infection) from control-theoretical viewpoint. Strong engagements and interests from Clinicians and Industries indicate the potential of our findings for future translational research. Our research was disseminated through the monthly magazine of National Eczema Society, the website of American Academy Of Allergy, Asthma & Immunology. |
First Year Of Impact | 2017 |
Sector | Education,Healthcare |
Impact Types | Societal |
Description | BBSRC Impact Acceleration Funding |
Amount | £14,909 (GBP) |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 11/2015 |
End | 06/2016 |
Description | British Skin Foundation Small Grant Awards |
Amount | £9,980 (GBP) |
Funding ID | 021/SG/17 |
Organisation | British Skin Foundation |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 10/2017 |
End | 09/2018 |
Description | EPSRC Impact Acceleration Account - Pathways to Impact |
Amount | £16,806 (GBP) |
Organisation | Imperial College London |
Sector | Academic/University |
Country | United Kingdom |
Start | 04/2018 |
End | 09/2018 |
Description | EPSRC Impact Award |
Amount | £21,476 (GBP) |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 10/2016 |
End | 03/2017 |
Description | Early prevention of progression of pre-school wheezing to school-age asthma by an integrated in silico, in vitro and in vivo approach |
Amount | £199,993 (GBP) |
Organisation | Action Medical Research |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 05/2021 |
End | 04/2023 |
Description | Forecasting atopic dermatitis disease activity using model-based machine learning |
Amount | £8,082,280 (GBP) |
Funding ID | 005/R/18 |
Organisation | British Skin Foundation |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 10/2019 |
End | 09/2021 |
Description | J&J PhD studentship |
Amount | £75,000 (GGP) |
Organisation | Johnson & Johnson |
Sector | Private |
Country | United States |
Start | 10/2012 |
End | 01/2016 |
Description | PhD studentship |
Amount | £90,000 (GBP) |
Funding ID | NC/P00217X/1 |
Organisation | National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) |
Sector | Public |
Country | United Kingdom |
Start | 10/2017 |
End | 09/2020 |
Description | RIKEN PhD studentship |
Amount | £85,000 (GBP) |
Organisation | RIKEN |
Sector | Public |
Country | Japan |
Start | 01/2014 |
End | 12/2017 |
Description | Research grant |
Amount | 9,980,000 kr. (DKK) |
Funding ID | LF16028 |
Organisation | LEO Foundation |
Sector | Charity/Non Profit |
Country | Denmark |
Start | 01/2017 |
End | 12/2019 |
Title | Control-theoretical framework for fly gaze stabilization control |
Description | We proposed a control-theoretical framework to understand how flies regulate the gaze. |
Type Of Material | Model of mechanisms or symptoms - non-mammalian in vivo |
Year Produced | 2010 |
Provided To Others? | Yes |
Impact | This model allowed us to quantitatively analyze the fly gaze control mechanisms, that will be useful to design biomimetic control systems. |
Title | Mathematical method to visualize the depth-dependent skin barrier profiles and barrier deficiencies |
Description | The method calculates the resistance of stratum cornuem (SC) to water diffusion along the SC depth, and thereby quantifies and visualises the depth-dependent barrier function, through integration of data of TEWL (Trans Epidermal Water Loss) and water concentration profiles measured by confocal Raman microspectroscopy. The method, for example, allows to quantify the subclinical damage in AD (atopic dermatitis) non-lesional skin and visualise by a depth-dependent barrier resistance profile. |
Type Of Material | Model of mechanisms or symptoms - human |
Year Produced | 2015 |
Provided To Others? | Yes |
Impact | To be evaluated. |
Title | Mathematical model of Aspergillus infection |
Description | This first mathematical model to understand the mechanism of aspergillus infection can predict the dynamics of fungal burden controlled by immune reactions. |
Type Of Material | Model of mechanisms or symptoms - human |
Year Produced | 2012 |
Provided To Others? | Yes |
Impact | The model allows us to investigate low-dose infection, which is difficult to be investigated in mice models. It will therefore reduce/replace animal experiments. This model also enhanced more quantitative understanding required for drug discovery. |
Title | Mathematical model of S. Pneumoniae infection |
Description | This ODE-based model describes the control mechanisms for S. Pneumoniae infection, especially the control mechanisms for epithelial barrier in the upper airway. |
Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
Year Produced | 2013 |
Provided To Others? | Yes |
Impact | This model replaces the animal experiments. |
URL | http://journal.frontiersin.org/article/10.3389/fphys.2017.00115/full |
Title | Mathematical model to understand mechanisms of atopic dermatitis |
Description | ODE-based model to describe the cellular- and tissue-level reactions that regulate skin barrier homeostasis and inflammation. |
Type Of Material | Model of mechanisms or symptoms - human |
Year Produced | 2011 |
Provided To Others? | Yes |
Impact | This first mathematical model has been widely appreciated by dermatologists and provides a framework to understand previous clinical and biological data. More and more quantitative data are being measured. |
Title | AD model |
Description | Mathematical model that describes the main mechanisms for onset of atopic dermatitis. |
Type Of Material | Computer model/algorithm |
Year Produced | 2011 |
Provided To Others? | Yes |
Impact | This model encourages quantitative and systems-level investigation for atopic dermatitis and its treatments. |
URL | http://www.jacionline.org/article/S0091-6749(16)31433-6/fulltext |
Title | Bacteria model |
Description | A mathematical model to investigate the role of epithelium barrier in bacterial infection in the upper airway. |
Type Of Material | Computer model/algorithm |
Year Produced | 2013 |
Provided To Others? | Yes |
Impact | It reduces the number of animal experiments. |
URL | http://journal.frontiersin.org/article/10.3389/fphys.2017.00115/full |
Title | Fungal model |
Description | A mathematical model that describes the host-pathogen interactions for A. fumigatus. |
Type Of Material | Computer model/algorithm |
Year Produced | 2012 |
Provided To Others? | Yes |
Impact | It had a big impact to reduce/replace animal experiments. |
URL | http://www.nature.com/articles/srep13958 |
Title | Plant stress response model |
Description | RD29A transcription model for Arabidopsis thaliana |
Type Of Material | Computer model/algorithm |
Year Produced | 2016 |
Provided To Others? | Yes |
Impact | This model will help to investigate the synergistic effects of activation of RD29A via integration of salinity stress and abscisic acid in Arabidopsis thaliana |
URL | https://academic.oup.com/pcp/article/57/10/2147/2755877/Synergistic-Activation-of-RD29A-Via-Integrat... |
Description | Mathematical modelling of regulatory mechanisms for skin barrier homeostasis |
Organisation | RIKEN |
Country | Japan |
Sector | Public |
PI Contribution | We develop the mathematical model to understand the onset and progression of atopic dermatitis. |
Collaborator Contribution | RIKEN IMS team developed transgenic mice which demonstrate symptoms of atopic dermatitis. They further conducted experiments using the developed AD mice and provided us the data needed for development of the mathematical model. |
Impact | Publication in preparation. |
Start Year | 2014 |
Description | Systems biology of Atopic dermatitis |
Organisation | Our Lady's Children's Hospital |
Department | National Children's Research Centre |
Country | Ireland |
Sector | Academic/University |
PI Contribution | We analyze the clinical data provided by our partner and use the results for development of mathematical model of atopic dermatitis. |
Collaborator Contribution | The partner collect the data from patients. |
Impact | Domínguez-Hüttinger E, Christodoulides P, Miyauchi K, Irvine AD, Okada-Hatakeyama M, Kubo M, Tanaka RJ, 2016, Mathematical modeling of atopic dermatitis reveals "double-switch" mechanisms underlying 4 common disease phenotypes., J Allergy Clin Immunol Latest Research Summaries for American Academy of Allergy Asthma and Immunology https://www.aaaai.org/global/latest-research-summaries/Current-JACI-Research/diagnosis-skin-allergy National Eczema Society magazine, March 2017, Mathematical modelling for better diagnosis and treatment of eczema Multi-disciplinary: Engineering, Dermatology |
Start Year | 2012 |
Description | Water control of skin |
Organisation | Johnson & Johnson |
Country | United States |
Sector | Private |
PI Contribution | We are developing mathematical models to understand the regulatory mechanisms of water control in skin. |
Collaborator Contribution | Scientific discussion at regular meetings; Data gathering. |
Impact | Multi-disciplinary: Control theory, computational biology, skin biology. |
Start Year | 2011 |
Description | Latest research (AAAAI) |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Latest research summaries described on the webpage of American Academy of Allergy Asthma & Immunology |
Year(s) Of Engagement Activity | 2016 |
URL | https://www.aaaai.org/global/latest-research-summaries/Current-JACI-Research/diagnosis-skin-allergy |
Description | National Eczema Society magazine |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | We wrote an article for the magazine published and distributed every month by the National Eczema Society. The article aimed to explain how our mathematical modelling approach could help eczema patients. |
Year(s) Of Engagement Activity | 2017 |
URL | http://www.eczema.org/departments/10 |
Description | Press release (Imperial news) |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | This article introduces the main results and impact of our published paper on new mathematical models of eczema pathogenesis. |
Year(s) Of Engagement Activity | 2016 |
URL | http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_24-11-2016-15-14-54 |
Description | School Visit (Lycee) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | We visited a primary school in Parsons Green to run a workshop, where 60 pupils tried a scientific game we developed, based on our research in understanding the regulatory mechanisms of atopic dermatitis. We also gave presentations about the science behind the atopic dermatitis. |
Year(s) Of Engagement Activity | 2016 |
Description | School Visit (Wimbledon) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | We visited a primary school in Wimbledon to run a workshop, where 60 pupils tried a scientific game we developed, based on our research in understanding the regulatory mechanisms of atopic dermatitis. We also gave presentations about the science behind the atopic dermatitis. |
Year(s) Of Engagement Activity | 2016 |