Use of transgenic zebrafish as a tool to study nanomaterial inflammogenicity

Lead Research Organisation: Heriot-Watt University
Department Name: Sch of Engineering and Physical Science

Abstract

This project will use zebrafish to assess the inflammatory responses induced by nanomaterials (NMs) in order to identify if zebrafish are a uesful (alternative) tool to investigate NM mediated inflammatory responses (e.g. neutrophil accumulation). A panel of NMs will be tested to identify whether the physico-chemical properties of NMs influence their pathogenicity. This will require that the physico-chemical properties of the NMs under investigation are characterised thoroughly (e.g. using AFM, TEM, SEM, ICP-MS). Where possible state of the art microscopy will be used to visualise and track immune cell movement in zebrafish models, and to quantify their accumulation. Of benefit, is that the ability of some of these NMs to induce pulmonary inflammation has already been tested in previous in vivo (rodent) studies. This will allow us to identify whether zebrafish are an appropriate alternative to rodent testing.

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509474/1 01/10/2016 30/09/2021
1813003 Studentship EP/N509474/1 01/10/2016 31/03/2020 Suzanne Gillies
 
Description Developing the transgenic zebrafish larvae as a model organism for nanotoxicology and investigating the use of alternative in vitro assays using human cells (primary neutrophils) and cell lines (HL-60 neutrophil-like cells)
Exploitation Route A protocol has been developed which utilises transgenic zebrafish larvae from 3dpf to 5dpf to assess neutrophil (inflammatory) responses to nanomaterials, either by microinjection or by tail fin wound assay. Further work is required to establish the optimal injection sites in larvae, otic vesicle is possible but is associated with high mortality. The tail fin wound should be further optimised as this assay has the potential to aid the investigation of the mechanism of nanomaterial toxicity and uptake/fate of nanomaterials, especially in other reporter strains (e.g. oxidative stress line).
Sectors Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description Investigation of the toxicity of Particulate Matter Emitted from Biomass Burning in Thailand 
Organisation Australian National University (ANU)
Country Australia 
Sector Academic/University 
PI Contribution There are uncertainties regarding the effects of haze pollution on human health in Thailand. This knowledge gap urgently needs to be addressed to inform the implementation of appropriate, evidence-based policy interventions by regional and national Governments that protect public health and improve the welfare of the population. Therefore our research project aims to investigate the toxicity of particulate matter (PM) emitted from biomass burning and compare this to the toxicity of PM emitted from other sources. HWU is responsible for assessing the toxicity of the PM samples (using in vitro and zebrafish embryo models)
Collaborator Contribution Collaborators in Thailand and Australia will provide PM samples. HWU will assess the toxictiy of the PM samples using in vitro and zebrafish models. The IOM will compare the findings obtained from the alternative models to existing epidemiological data to identify if these models make a good prediction of toxicity.
Impact The project has only recently started and so no data has been collected yet. The project is extremely multidiscplinary involving toxicologists, exposure scientists, and epidemiologists. We are also engaging with interested stakeholders (e.g. policy makers in the Thai Government) at an early stage of the project to ensure they are kept abreast of project outcomes. Our international, multidisciplinary team will investigate how harmful different sources of pollution are in Thailand to inform the introduction of interventions to protect the health of vulnerable communities. We will share expertise between research groups and supporting the training and education of early career researchers.
Start Year 2020
 
Description Investigation of the toxicity of Particulate Matter Emitted from Biomass Burning in Thailand 
Organisation Chiang Mai University
Country Thailand 
Sector Academic/University 
PI Contribution There are uncertainties regarding the effects of haze pollution on human health in Thailand. This knowledge gap urgently needs to be addressed to inform the implementation of appropriate, evidence-based policy interventions by regional and national Governments that protect public health and improve the welfare of the population. Therefore our research project aims to investigate the toxicity of particulate matter (PM) emitted from biomass burning and compare this to the toxicity of PM emitted from other sources. HWU is responsible for assessing the toxicity of the PM samples (using in vitro and zebrafish embryo models)
Collaborator Contribution Collaborators in Thailand and Australia will provide PM samples. HWU will assess the toxictiy of the PM samples using in vitro and zebrafish models. The IOM will compare the findings obtained from the alternative models to existing epidemiological data to identify if these models make a good prediction of toxicity.
Impact The project has only recently started and so no data has been collected yet. The project is extremely multidiscplinary involving toxicologists, exposure scientists, and epidemiologists. We are also engaging with interested stakeholders (e.g. policy makers in the Thai Government) at an early stage of the project to ensure they are kept abreast of project outcomes. Our international, multidisciplinary team will investigate how harmful different sources of pollution are in Thailand to inform the introduction of interventions to protect the health of vulnerable communities. We will share expertise between research groups and supporting the training and education of early career researchers.
Start Year 2020
 
Description Investigation of the toxicity of Particulate Matter Emitted from Biomass Burning in Thailand 
Organisation Institute of Occupational Medicine (IOM)
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution There are uncertainties regarding the effects of haze pollution on human health in Thailand. This knowledge gap urgently needs to be addressed to inform the implementation of appropriate, evidence-based policy interventions by regional and national Governments that protect public health and improve the welfare of the population. Therefore our research project aims to investigate the toxicity of particulate matter (PM) emitted from biomass burning and compare this to the toxicity of PM emitted from other sources. HWU is responsible for assessing the toxicity of the PM samples (using in vitro and zebrafish embryo models)
Collaborator Contribution Collaborators in Thailand and Australia will provide PM samples. HWU will assess the toxictiy of the PM samples using in vitro and zebrafish models. The IOM will compare the findings obtained from the alternative models to existing epidemiological data to identify if these models make a good prediction of toxicity.
Impact The project has only recently started and so no data has been collected yet. The project is extremely multidiscplinary involving toxicologists, exposure scientists, and epidemiologists. We are also engaging with interested stakeholders (e.g. policy makers in the Thai Government) at an early stage of the project to ensure they are kept abreast of project outcomes. Our international, multidisciplinary team will investigate how harmful different sources of pollution are in Thailand to inform the introduction of interventions to protect the health of vulnerable communities. We will share expertise between research groups and supporting the training and education of early career researchers.
Start Year 2020
 
Description Investigation of the toxicity of Particulate Matter Emitted from Biomass Burning in Thailand 
Organisation Mahidol University
Country Thailand 
Sector Academic/University 
PI Contribution There are uncertainties regarding the effects of haze pollution on human health in Thailand. This knowledge gap urgently needs to be addressed to inform the implementation of appropriate, evidence-based policy interventions by regional and national Governments that protect public health and improve the welfare of the population. Therefore our research project aims to investigate the toxicity of particulate matter (PM) emitted from biomass burning and compare this to the toxicity of PM emitted from other sources. HWU is responsible for assessing the toxicity of the PM samples (using in vitro and zebrafish embryo models)
Collaborator Contribution Collaborators in Thailand and Australia will provide PM samples. HWU will assess the toxictiy of the PM samples using in vitro and zebrafish models. The IOM will compare the findings obtained from the alternative models to existing epidemiological data to identify if these models make a good prediction of toxicity.
Impact The project has only recently started and so no data has been collected yet. The project is extremely multidiscplinary involving toxicologists, exposure scientists, and epidemiologists. We are also engaging with interested stakeholders (e.g. policy makers in the Thai Government) at an early stage of the project to ensure they are kept abreast of project outcomes. Our international, multidisciplinary team will investigate how harmful different sources of pollution are in Thailand to inform the introduction of interventions to protect the health of vulnerable communities. We will share expertise between research groups and supporting the training and education of early career researchers.
Start Year 2020
 
Description Brightest Watts - practical demonstration of alternative models to schoolchildren 2019 
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 Schoolchildren participated in practical work during 2, 2.5 hour sessions as part of the HWU Brightest Watts summer week which allowed them to gain experience of working with in vitro and zebrafish models. This was also an opportunity to educate schoolchildren about the need to find alternatives to animal testing.
Year(s) Of Engagement Activity 2019
 
Description Invited to talk at the NC3Rs PhD studentship Information Day 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact An overview of the research project was provided to academics hoping to apply for NC3Rs PhD studentships - this will hopefully promote the more widespread use of the model.
Year(s) Of Engagement Activity 2019
 
Description Organisation of session on Alternatives to Animal Testing as part of the Health Innovation and Technologies Conference at HWU 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact I arrange the Alternatives to Animal Testing session as part of the Health Innovation Technologies Conference at HWU. This allowed researchers to showcase their research to a range of interested stakeholders (e.g. academics, students, industry, policy makers, funders, patients, general public).
Year(s) Of Engagement Activity 2019
 
Description Participation in Explorathon event in Edinburgh 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact We had a stall at the Explorathon event in the botanical gardens in Edinburgh where we gave practical demonstrations of lab work (Related to the use of alternative models in research). Children (a range of ages), their parents and members of the public attended the event
Year(s) Of Engagement Activity 2019
 
Description Poster Presentation at the First COST Action CA17140 training school "Cancer and Nanomedicine", Italy (2019) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact This training event allowed research activities to be communicated to other researchers working in the field of nanotoxicology and nanomedicine - this increased awareness of the alternative models employed in the project amongst the scientific community.
Year(s) Of Engagement Activity 2019
 
Description Poster presentation at 'The Nanosafety Forum for Young Scientists' (Malta, September 2018) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact A poster presentation which provided an overview of the research findings was given at The Nanosafety Forum for Young Scientists', (Malta)
Year(s) Of Engagement Activity 2018
 
Description Poster presentation at 12th International Particle Toxicology Conference (Austria) 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Poster presentation at the 12th International Particle Toxicology Conference, Austria allowed research activities to be communicated to the scientific community, and industry.
Year(s) Of Engagement Activity 2019
 
Description Poster presentation at the symposium "Fish and amphibian embryos as alternative models in toxicology and teratology" (Paris, December 2018) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact A poster was presented which provided an overview of the research findings of the project so far
Year(s) Of Engagement Activity 2018
 
Description Poster presented at the 12th International Particle Toxicology Conference in Austria 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact I presented a poster at this conference
Year(s) Of Engagement Activity 2019
 
Description Poster presented at the First COST Action CA17140 training school "Cancer and Nanomedicine" in Italy 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact I attended a training school which focused on nanomedicine safety assessment. I presented a poster of my research to share with the other participants of the school.
Year(s) Of Engagement Activity 2019
 
Description Presentation at the HWU Festival of Research 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact I provided a presentation as part of the HWU Festival of Research as part of the session on Health Innovation and Technology. This talk discussed how alternative models could be used to a greater extent in biomedical research.
Year(s) Of Engagement Activity 2019
 
Description Presentation to the U3A (University for the 3rd Age 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact A presentation entitled 'The benefits and limitations of employing alternative, non-rodent models to investigate the toxicity of nanomaterials' was given to attendees in order to provide an overview of how alternative, non rodent models can be employed in nanotoxicology testing
Year(s) Of Engagement Activity 2019
 
Description Teaching of Undergraduate and Postgraduate Students 2019/2020 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact As part of several of my BSc and MSc courses I have included lectures on the 3Rs principles and use of alternative models in biomedical research. I have also supervised final year BSc students who are conducting laboratory or desk based projects which employ alternative, non rodent models.
Year(s) Of Engagement Activity 2019,2020