Experiencing the micro-world - a cell's perspective
Lead Research Organisation:
Heriot-Watt University
Department Name: Sch of Engineering and Physical Science
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Organisations
- Heriot-Watt University (Lead Research Organisation)
- Medical Research Council (Co-funder)
- Biotechnology and Biological Sciences Research Council (Co-funder)
- UNIVERSITY OF NOTTINGHAM (Collaboration)
- University of St Andrews (Collaboration)
- University of Adelaide (Collaboration)
- UNIVERSITY OF LIVERPOOL (Collaboration)
Publications
Ashworth JC
(2020)
Peptide gels of fully-defined composition and mechanics for probing cell-cell and cell-matrix interactions in vitro.
in Matrix biology : journal of the International Society for Matrix Biology
Ferraro R
(2023)
Compressional stress stiffening & softening of soft hydrogels - how to avoid artefacts in their rheological characterisation
in Soft Matter
Guadayol Ò
(2021)
Microrheology reveals microscale viscosity gradients in planktonic systems.
in Proceedings of the National Academy of Sciences of the United States of America
James JR
(2023)
Hydrogel-Based Pre-Clinical Evaluation of Repurposed FDA-Approved Drugs for AML.
in International journal of molecular sciences
Khalid MA
(2019)
Computational Image Analysis of Guided Acoustic Waves Enables Rheological Assessment of Sub-nanoliter Volumes.
in ACS nano
Matheson A
(2021)
Microrheology With an Anisotropic Optical Trap
in Frontiers in Physics
Matheson AB
(2021)
Optical Tweezers with Integrated Multiplane Microscopy (OpTIMuM): a new tool for 3D microrheology
in Scientific Reports
Matheson AB
(2021)
Optical Tweezers with Integrated Multiplane Microscopy (OpTIMuM): a new tool for 3D microrheology.
in Scientific reports
Mendonca T
(2023)
OptoRheo: Simultaneous in situ micro-mechanical sensing and imaging of live 3D biological systems
in Communications Biology
Moreno-Guerra JA
(2019)
Model-Free Rheo-AFM Probes the Viscoelasticity of Tunable DNA Soft Colloids.
in Small (Weinheim an der Bergstrasse, Germany)
Rivas-Barbosa R
(2020)
i-Rheo: determining the linear viscoelastic moduli of colloidal dispersions from step-stress measurements.
in Physical chemistry chemical physics : PCCP
Smid P
(2019)
Detection of a common odd aberration in confocal reflection microscopy by means of an edge scan
in Journal of Optics
Smith M
(2023)
Machine learning opens a doorway for microrheology with optical tweezers in living systems
in AIP Advances
Tassieri M
(2019)
Microrheology with optical tweezers: peaks & troughs
in Current Opinion in Colloid & Interface Science
| Description | This work aims to develop a new instrument capable of imaging cells live in 3D culture over a long time course whilst mapping to these images local readings of the viscosity and elasticity of the matrix next to the cells. Our progress so far has been to build a novel light sheet microscope that is fully beam scanning and the sample remains stationary throughout imaging. This has allowed us to image the same 3D cluster of live cells over a 5 day period. In parallel we have developed a new approach to optical trapping micro-rheology that allows the viscosity and elasticity to be characterised in 3D as opposed to the 2D that was previously possible. We have published data that demonstrates our ability to use micro-rheology methodologies to characterise the material properties of peptide hydrogel comparing our readings to those taken with a more traditional oscillatory rheometer. Working on this project are 4 researchers (3 PDRAs and 1 technician) who are developing important multi-disciplinary skills working with a project team that spans Medicine, Engineering, Physics and Pharmacy. New research questions have opened up in collaboration with the University of Lincoln in Marine Biology studying the local viscosity gradients surrounding plankton. |
| Exploitation Route | The final platform, NuSense, has been successfully designed and implemented and sued for several end goal biological observations. Spin off work focussing on key elements ahs also advanced experimental and analytical approaches related to the work. |
| Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |
| Description | Guidance from NC3Rs on non-animal derived matrices |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Contribution to new or Improved professional practice |
| URL | https://nc3rs.org.uk/3rs-resources/replacing-basement-membrane-extracts-bmes |
| Description | Exploring the role of matrix encapsulation on early developmental decisions using non-animal sourced hydrogels |
| Amount | £120,000 (GBP) |
| Funding ID | NC/W001918/1 |
| Organisation | National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2022 |
| End | 01/2026 |
| Description | Fully humanised 3D vascular perfused model for breast cancer modelling and therapeutic screening |
| Amount | £75,911 (GBP) |
| Funding ID | NC/T001259/1 |
| Organisation | National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2019 |
| End | 09/2021 |
| Description | Innovation to commercialisation of university research (ICURe) Nottamouse project |
| Amount | £40,000 (GBP) |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 06/2022 |
| End | 12/2022 |
| Description | Investigating the Biophysical Properties of Chromosomes |
| Amount | £180,000 (GBP) |
| Organisation | The Leverhulme Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 11/2021 |
| End | 11/2024 |
| Description | Lighting the Way to a Healthy Nation - Optical 'X-rays' for Walk Through Diagnosis & Therapy |
| Amount | £5,577,754 (GBP) |
| Funding ID | EP/T020997/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 06/2020 |
| End | 05/2025 |
| Description | Nano-plasmonics for healthcare |
| Amount | £12,000 (GBP) |
| Organisation | University of Nottingham |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 01/2019 |
| End | 01/2021 |
| Description | Optimising human stem cell models to decipher signals and responses during organogenesis |
| Amount | £196,734 (GBP) |
| Organisation | National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2023 |
| End | 02/2025 |
| Description | Replacing the need for patient-derived xenografts and matrigel organoid culture as preclinical models for breast cancer |
| Amount | £75,591 (GBP) |
| Funding ID | NC/T001267/1 |
| Organisation | National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) |
| Sector | Public |
| Country | United Kingdom |
| Start | 07/2019 |
| End | 06/2020 |
| Description | Squeezing the most out of DNA; developing nanoconfinement tools to study DNA repair |
| Amount | £90,000 (GBP) |
| Organisation | The Royal Society |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 10/2019 |
| End | 04/2022 |
| Description | U-care: Deep ultraviolet light therapies |
| Amount | £6,132,366 (GBP) |
| Funding ID | EP/T020903/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 06/2020 |
| End | 06/2025 |
| Description | Understanding How Matrix Remodelling & Respiratory Infection Impact Progression Of Idiopathic Pulmonary Fibrosis Using Stem Cell Derived Alveolar Cells |
| Amount | £93,000 (GBP) |
| Organisation | British Lung Foundation (BLF) |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 09/2019 |
| End | 08/2022 |
| Title | Peptide gels for 3D breast cancer models |
| Description | Current materials used for in vitro disease models are often limited by their poor similarity to human tissue, batch-to-batch variability and high complexity in composition and manufacture. We have developed a "blank slate" culture environment that can be customized by incorporating matrix components specifically selected to match the target tissue, with mechanical properties controlled independently and simultaneously. Based on a self-assembling peptide hydrogel, this system contains no exogenous proteins or glycosaminoglycans: only those specifically added, or those synthesized by the cells in culture. This 3D culture platform therefore provides full control over biochemical and physical properties, allowing the composition and mechanics of the tissue of interest to be recapitulated in vitro. As proof-of-concept, we designed a panel of hydrogels designed to mimic the stages of breast cancer progression. Controlling the peptide gelator concentration allows hydrogel stiffness to be matched to normal breast (<1 kPa) or breast tumour (>1 kPa), with higher stiffness favouring the viability of breast cancer cells over normal breast cells. In parallel, these hydrogels may be modified with matrix components relevant to human breast, such as collagen I and hyaluronan. The choice and concentration of these additions control the size, shape and organisation of the breast epithelial cell structures formed in co-culture with fibroblasts. This system therefore provides a means of unravelling the individual influences of matrix, mechanical properties and cell-cell interactions in cancer and disease. |
| Type Of Material | Model of mechanisms or symptoms - human |
| Year Produced | 2018 |
| Provided To Others? | Yes |
| Impact | We have presented the gel technology at events specifically designed to encourage uptake by other researchers working in this area (e.g. BACR meeting in Leeds, May 2018) and have trained researchers from other groups to encourage uptake of the technology. These training visits were supported financially by NC3Rs. We have also developed additional collaborations related to this technology including with a commercial partner able to provide the raw materials required for the gels. By demonstrating the applicability of the peptide gels to breast cancer modelling we have also attracted additional collaborations with groups working on fibrosis and the support of stem cell differentiation. |
| Description | Adelaide Nottingham Joint PhD Studentship |
| Organisation | University of Adelaide |
| Country | Australia |
| Sector | Academic/University |
| PI Contribution | A new joint PhD student started in January 2021. The student will be supervised by Kylie Dunning and Amanda Wright and will spend years 1 and 3 in Adelaide and year 2 in Nottingham |
| Collaborator Contribution | Initial contact was made via Kylie Dunning and we then applied jointly for this studentship. |
| Impact | PhD studentship |
| Start Year | 2020 |
| Description | Alan Huett - joint PhD student |
| Organisation | University of Nottingham |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Joint PhD student - William Hardiman |
| Collaborator Contribution | Joint PhD student - William Hardiman |
| Impact | - |
| Start Year | 2019 |
| Description | Alan Huett - joint PhD student |
| Organisation | University of Nottingham |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Joint PhD student - William Hardiman |
| Collaborator Contribution | Joint PhD student - William Hardiman |
| Impact | - |
| Start Year | 2019 |
| Description | Anna Kotowska |
| Organisation | University of Nottingham |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Anna Kotowska has been awarded an EPSRC doctoral prize that will use the instrumentation and methods developed during this project. |
| Collaborator Contribution | Anna Kotowska has been awarded an EPSRC doctoral prize that will use the instrumentation and methods developed during this project. |
| Impact | - |
| Start Year | 2022 |
| Description | Claire Friel - Joint PhD Student |
| Organisation | University of Nottingham |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Joint PhD student - William Hardiman |
| Collaborator Contribution | Joint PhD student - William Hardiman |
| Impact | N/A |
| Start Year | 2019 |
| Description | David Turner |
| Organisation | University of Liverpool |
| Department | School of Life Sciences Liverpool |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I provide matrix biology expertise and the use of hydrogels for 3D culture |
| Collaborator Contribution | David provides his developmental biology expertise, tools and experience |
| Impact | David is CoI on our NC3Rs studentship |
| Start Year | 2021 |
| Description | Joint PhD student with Kishan Dholakia |
| Organisation | University of St Andrews |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have a joint student under the Nottingham and Adelaide Studentship scheme |
| Collaborator Contribution | With Kylie Dunning at the University of Adelaide we were awarded a joint PhD studentship via the Nottingham and Adelaide partnership. Kishan Dholakia is on secondment at the University of Adelaide and is part of the supervisory team. The student started in January 2021. |
| Impact | PhD student started in January 2021 |
| Start Year | 2020 |
| Description | School talk |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | 4th December 2019: Lynn Paterson gave a talk to around 30 students from Kinross High School, about her research 'Shedding new light on biology' and spent 5 minutes of the 1 hour talk discussing the ideas around our nusense project. |
| Year(s) Of Engagement Activity | 2019 |
| Description | School talk |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | 13th November 2019: Lynn Paterson gave a talk to around 70 students from Grantown Grammar School, Grantwon on Spey, around her research area 'Shedding new light on biology' and spent 5 minutes of the 1 hour talk discussing the ideas around our nusense project. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Science in the Park |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | The activity was a science festival in Nottingham run by the University of Nottingham and Nottingham Trent University. It was mostly aimed at families. Our research group had a stand called 'Light up the Park'. |
| Year(s) Of Engagement Activity | 2022 |
| Description | Scientific conference - Optical Trapping and Optical Manipulations, SPIE - Invited talk |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Invited talk at an international scientific conference |
| Year(s) Of Engagement Activity | 2021 |