Nanoniche - The use of microRNAs and nanotopography to modulate skeletal stem cell fate and function

Lead Research Organisation: University of Glasgow
Department Name: College of Medical, Veterinary, Life Sci

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.

Technical Summary

With an increasing ageing population the clinical requirement to replace degenerated tissues, such as musculoskeletal tissue, is a major socio-economic requirement.

Skeletal (SSC) or Mesenchymal Stem Cells (MSCs) have the potential to form a variety of stromal lineages including bone, cartilage, fat and muscle and display plasticity between lineages. Lineage modulation offers significant therapeutic potential for using these cells in regenerative medicine. A key issue is an understanding of skeletal stem cell differentiation and maintenance of skeletal stem cell properties.

MicroRNAs (miRNAs) are a class of endogenous non-protein-coding single-stranded RNAs, ranging from 18-25 nucleotides in length that regulate gene transcription post-transcriptionally with fundamental and diverse roles in a variety of biological and pathological processes. A number of miRNAs are specifically expressed in stem cells, control stem cell self-renewal and differentiation, while other miRNAs have been linked with disease or prognosis. We have emergent proof of concept data that miRNAs regulate skeletal stem cell fate and function. We propose that miRNAs play a critical role in the regulation of skeletal stem cell fate and function.

We will determine the role of miRNAs in the maintenance of stem phenotype or enhancement of bone stem cell differentiation and mechanisms involved including cytoskeletal or epigenetic changes. We have recently shown that defined nanotopographies are capable of robustly regulating SSC fate in the absence of chemical cues. We will therefore use custom designed nanotopographies to control SSC phenotype (for instance, to induce osteogenesis or maintain SSC numbers) and examine how miRNAs affect stem cell responses through modulation of epigenetic, biochemical and biomechanical processes.

This study will facilitate our understanding of the mechanisms involved in the regulation of skeletal stem cell fate and function.

Planned Impact

Our research project aims to bring together a multidisciplinary team to elucidate the role of microRNAs in the regulation of skeletal stem cell fate and function, and will have a number of academic, industrial, societal, economic and awareness impacts.

ACADEMIA
Many optional training opportunities will be available to the Research Fellow, Dr Carmen de Andres - RO was, until August 2013, Associate Dean International and Enterprise at the University of Southampton and thus has seven years' experience in being able to tie in with the aims of the RC UK, to develop entrepreneurship within the academic culture and the development of enterprise skills for researchers that will further enhance Dr de Andres and critically, the impact of the research from this project grant. We will engage on an international basis to promote the UK as a centre of excellence in all aspects of stem cells, microRNA/epigenetic and regenerative medicine.

Our track records show evidence of impact in Japan (joint publications, student research exchange with Kyoto University (Oreffo-Tabata); Europe (Leverhulme visiting fellowship - Oreffo to Dr de Andres Catalonia University), Middle East (Oreffo adjunct chair and joint research programmes at Stem Cell Unit, King Saud University, China /Hong Kong (Joint Stem Cell lab between Centre for Human Development, Stem cells and regeneration and Chinese University of Hong Kong) and many other linkages.

BUSINESS AND INDUSTRY
We have a number of industry links (see track record for ROCO, NG and MD) and will communicate openly with appropriate industry partners (IP discussions will be undertaken under CDAs) especially towards the final phase of our programme as we develop robust strategies for growth factor delivery from our various scaffolds for tissue regeneration. See 'Pathways to Impact' for more details. ROCO established the University of Southampton Health and Pharma Industry Sector Theme (Director 2011-2013) and will utilise established links in this programme.

GENERAL PUBLIC - PUBLIC AWARENESS AND POLICY
We will engage with the general public to explain sensitively (management of expectation is key in this area of research) the clinical and commercial potential of our work. We believe that stem cell biology and the life sciences - encapsulated by our project have a special responsibility to explain stem cell science to schoolchildren. There is significant potential in this area including vast potential from a reparative standpoint for bone stem cells in orthopaedics and skeletal stem cell biology across a range of clinical areas and the importance of multidisciplinary science - our outreach programme will provide impact over the next 3 years through active schools outreach by ROCO and all the applicants.

GENERAL PUBLIC - HEALTH AND WELL-BEING
TSB Cell Therapy Catapult Centre: We will engage with the Cell Therapy Catapult as appropriate especially from a stem cell clinical translation perspective in the end phase of our programme again as appropriate (preclinical and early clinical development).
Improving Public Services: Oreffo, Dalby and Gadegaard work closely with the clinical community (see Pathways to Impact) including specifically the orthopaedic community (RO - 7 clinical MD/PhD trained in the last eight years and over 30 papers and 20 awards to clinical fellows) - we will look to translate our stem cell science to through to the clinic, if appropriate, in regenerative projects, programmes as appropriate including the UK Regenerative Medicine and Medical Technologies Innovation and Knowledge Centre programmes.

Publications

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Harper MM (2018) Biogelx: Cell Culture on Self-Assembling Peptide Gels. in Methods in molecular biology (Clifton, N.J.)

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Grigoriou E (2017) Cell migration on material-driven fibronectin microenvironments. in Biomaterials science

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Ballester-Beltrán J (2017) Confined Sandwichlike Microenvironments Tune Myogenic Differentiation. in ACS biomaterials science & engineering

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Donnelly H (2018) Current approaches for modulation of the nanoscale interface in the regulation of cell behavior. in Nanomedicine : nanotechnology, biology, and medicine

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Al-Jarsha M (2018) Engineered Coatings for Titanium Implants To Present Ultralow Doses of BMP-7. in ACS biomaterials science & engineering

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Cheng ZA (2019) Nanoscale Coatings for Ultralow Dose BMP-2-Driven Regeneration of Critical-Sized Bone Defects. in Advanced science (Weinheim, Baden-Wurttemberg, Germany)

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Dalby M (2018) Receptor control in mesenchymal stem cell engineering in Nature Reviews Materials

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Nikukar H (2015) Stem-Cell Nanoengineering

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Salmerón-Sánchez M (2016) Synergistic growth factor microenvironments in Chemical Communications

 
Description That microRNAs can be used to target bone differentiation.
Exploitation Route License of the technology or sharing of the technology.
Sectors Healthcare

Pharmaceuticals and Medical Biotechnology

 
Description MicroRNAs are starting to find use in clinical trials and they are thus of interest to the public. We have used information from his grant in outreach activities engaging the public.
First Year Of Impact 2018
Sector Education,Healthcare
Impact Types Societal

 
Description Glasgow Orthopaedic Research Initiative
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Healickick (EU grant) translational day
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact Preparing surgeons for the technologies and getting advice how to best present the technologies in product form
 
Description Organisation of industry focussed stakeholder day
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Research Together - Patient and Public Involvement and Engagement Day 2023
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
Impact Patients have fed back very positively about the day and about what they had learnt about emerging science in the area they are interested in and also future technologies.
 
Description 'EPSRC and SFI Centre for Doctoral Training in Engineered Tissues for Discovery, Industry and Medicine
Amount £7,013,578 (GBP)
Funding ID EP/S02347X/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 05/2019 
End 12/2027
 
Description Engineering growth factor microenvironments - a new therapeutic paradigm for regenerative medicine
Amount £3,661,144 (GBP)
Funding ID EP/P001114/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 09/2016 
End 09/2022
 
Description Nanoparticle-Mediated microRNA Delivery for Increased Osteogenesis in a 3D Osteoporotic Bone Marrow Model
Amount £243,592 (GBP)
Funding ID TCS/18/25 
Organisation Chief Scientist Office 
Sector Public
Country United Kingdom
Start 03/2019 
End 02/2021
 
Title microRNAs 
Description Nanoparticle tagged microRNAs to turn on bone formation 
Type Of Material Technology assay or reagent 
Year Produced 2017 
Provided To Others? No  
Impact At present this is an in-house tool, but we will soon publish and work to make it available to research groups. 
 
Description COllaboration with Atelerix 
Organisation Atelerix
Country United Kingdom 
Sector Private 
PI Contribution Thi sis a joint PhD project in which we are designing in vitro stem cell niches
Collaborator Contribution Provision and tailoring of hydrogel materials
Impact Early collaboration
Start Year 2021
 
Description Collaboration with Bone Cancer Research Trust 
Organisation Bone Cancer Research Trust
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution We are developing models of sarcoma that are useful for bone cancer research
Collaborator Contribution They are supporting us with training placements, access to patients and advice.
Impact Development of better tissue models and enhanced training.
Start Year 2020
 
Description Collaboration with Cell Guidance Systems 
Organisation Cell Guidance Systems Ltd
Country United Kingdom 
Sector Private 
PI Contribution We started working together through the lifETIME CDT and now we have a KTP together working on enhancing hydrogels with Growth Factors. We provide cell expertise.
Collaborator Contribution They provide materials expertise.
Impact New product coming 2021
Start Year 2019
 
Description Souhtampton Collaboration 
Organisation University of Southampton
Department Bone and Joint Research Group
Country United Kingdom 
Sector Academic/University 
PI Contribution This is a long term collaboration where cells, materials and expertise are shared to drive research
Collaborator Contribution This is a long term collaboration where cells, materials and expertise are shared to drive research
Impact A large number of papers, grants and IP.
 
Description collaboration with Portugal 
Organisation University of Aveiro
Country Portugal 
Sector Academic/University 
PI Contribution We have exchanges people, skills and expertise
Collaborator Contribution We have exchanges people, skills and expertise
Impact Contributed towards PhD thesis and publication
Start Year 2023
 
Description ARCADIA public engagement 
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 ARCadia, was a festival of public events that celebrated the public opening of the ARC from 16-30 September 2022 that attracted almost 7000 people.
The general aims were:
Collaboration between the university and non-academic groups
A mix of disciplines, from the arts to social, physical and life sciences
Engaging traditionally marginalised groups, or groups who experience barriers to accessing the university
Engaging communities local to the ARC (postcodes G11, G3, G12)
75 free events for all ages were held day and night in the ARC, from schools workshops to cinema screenings, exhibitions, comedy, gaming, talks and even an outdoor ceilidh with dancing dinosaurs. Over 63% of events involved working in partnership with non-academic groups.
An astonishing number of people helped organise and run ARCadia events (and our group CeMi was central in this) , including 326 UofG colleagues, 147 students, 239 partner staff, 30 volunteers and for student interns.
The event attracted public visitor of all ages throughout the 2 weeks and everyone provided good comments and they would like to be able to experience an event like that in the future.
Year(s) Of Engagement Activity 2022
URL https://www.gla.ac.uk/myglasgow/news/newsarchive/2022/8november2022/headline_893700_en.html
 
Description Cell block science 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact Presented at prisoner outreach day at HMP Shotts
Year(s) Of Engagement Activity 2019
 
Description Centre for Doctoral Training Retreat 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Retreat to The Burn for formal PGR student training in entrepreneurship
Year(s) Of Engagement Activity 2021
 
Description Conference organisation CCE-GLORI 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact The local CCE-GLORI workshop is organised by Dr Monica P. Tsimbouri every year. It is a workshop where postgraduate students present their work to their peers and supervisors and discussion then follows the talks.
This is highly beneficial to students and promotes collaboration.
Year(s) Of Engagement Activity 2019
 
Description Conference organisation-GLORI2020 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Dr Monica P. Tsimbouri organises GLORI bi-annually. This conference encourages collaboration between the basic sciences, applied sciences, engineering and clinic. This has the aim of bringing the latest ideas in basic materials research into use to deliver the next-generation of orthopaedic care. It combines expertise from orthopaedic surgeons, plastic surgeons, biologists, engineers and chemists.
The conference is free for attendance and involves oral and poster presentations from professionals, scientists, clinicians and postgraduate students. It is always well attended.
It is sponsored by industry who are also involved in the conference.
Year(s) Of Engagement Activity 2020
 
Description European Society for Biomaterials Keynote (Dalby) Talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Keynote conference talk
Year(s) Of Engagement Activity 2021
 
Description GLORI 2023 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Meeting of the Glasgow Orthopaedic Research Initiative Tuesday 21st March 2023, ARC, GU.
An educational and collaborative meeting/workshop between Scientists and Clinicians.
This is a repeating workshope every year with the aim to inform everyone about new developemnt on bone regeneration.
Year(s) Of Engagement Activity 2023
 
Description GLORI conference organisation 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Planning and Organisation of Dr Monica P Tsimbouri the scientific mentor of the Glasgow Orthopaedic Research Initiative (GLORI). GLORI has been established to encourage collaboration between the basic sciences, applied sciences, engineering and clinic. This has the aim of bringing the latest ideas in basic materials research into use to deliver the next-generation of orthopaedic care. It combines expertise from orthopaedic surgeons, biologists, engineers and chemists not only from Glasgow and Strathclyde Universities but the rest of Scotland too and also with the view to expand to the rest of the UK.
Year(s) Of Engagement Activity 2018
 
Description GLORI-2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact National orthopedic conference in Glasgow where about 60 audience attended.
Year(s) Of Engagement Activity 2018
 
Description Glasgow Science Festival: Regenerate 
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 Glasgow Science Festival runs for a few weeks and we did a full day focusing on Stem Cell activities, talking to the general public (mainly children). The aim was teach them how stem cells differentiate.
Year(s) Of Engagement Activity 2021
 
Description HEALIKICK Translation session 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Translation session as part of the HEALIKICK project where clinicians from Spain attended to discuss emerging translational technologies.
Year(s) Of Engagement Activity 2023
 
Description Healickick (EU grant) translation day 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Discussion between academics and surgeons around technologies we have developed.
Year(s) Of Engagement Activity 2021
 
Description Industry seminar 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Attended seminar by CEO, John Sharpe of Cytonome (partner of the lifETIME CDT).
Year(s) Of Engagement Activity 2023
 
Description Invited talk at British Orthopaedic Research Society 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Discussed research training of junior surgeons
Year(s) Of Engagement Activity 2021
 
Description Joint CDT & UKANet/ECMage network meeting. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Joint conference of the lifETIME CDT and ECMage & Blast Networks met to hold a conference on topics aligned to the CDT & Networks followed by an EDI facilitated session.
Year(s) Of Engagement Activity 2024
 
Description Keynote talk (Dalby) at Tissue Engineerign and Regenerative medicien International Society 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Keynote talk at a major conference
Year(s) Of Engagement Activity 2021
 
Description Media interest BBC (nanokicking) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Talk sparked public interest

Many interested enquirers.
Year(s) Of Engagement Activity 2012
 
Description Media interest BBC (orthopaedic materials) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Sparked public interest

Enquieries from the public
Year(s) Of Engagement Activity 2013
 
Description Media interest BBC (stem cell growth) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Talk sparked public interest

Enquieries from the public
Year(s) Of Engagement Activity 2011
 
Description Nanotoxicology Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Invited talk for the Naotoxicology Society
Year(s) Of Engagement Activity 2016
 
Description Plenary talk at TERMIS 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Matthew Dalby gave a plenary talk on materials for stem cell growth and differentiation
Year(s) Of Engagement Activity 2023
 
Description Presentation at Joint ECMage/LifETIME CDT meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Keynote talk by Matthew Dalby.
Year(s) Of Engagement Activity 2024
 
Description Press release 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact STV and BBC news released an interview with Prof Matthew Dalby on the awards of two new major grants that would enable us to learn how we can better predict leukaemia (blood cancer) occurrence, as well as develop improved drug screening pathways to treat the disease, through a major funding boost worth £12million.
Year(s) Of Engagement Activity 2023
 
Description ResearchTogether: Patients Guiding the Future of Science 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact This was a Patient and Public Involvement & Engagement event that brought together patients, researchers, and charities to discuss recent research advancements as well as how to improve research targeting healthcare improvement in the future.
Year(s) Of Engagement Activity 2023
URL https://lifetime-cdt.org/agenda-of-cdt-events/research-together/
 
Description Royal Society of Chemistry Biomaterials Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Conference presentation
Year(s) Of Engagement Activity 2017
 
Description Science Den 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Professor Matthew Dalby on judging panel for the lifETIME CDT Science Den Competition
Year(s) Of Engagement Activity 2023
 
Description Scottish Metabolomics Network 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Invited talk
Year(s) Of Engagement Activity 2016
 
Description TCES 2010 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation paper presentation
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Dr Monica P Tsimbouri. exiting discussion after talk

Interested parties continued discussion
Year(s) Of Engagement Activity 2010
 
Description TCES 2012 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation paper presentation
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Dr P Tsimbouri. talk sparked questions and discussion afterwards

Engagement with company Reps and received very good discount on equipment.
Year(s) Of Engagement Activity 2012
 
Description TERMIS EU 2011 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation paper presentation
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Dr Monica P Tsimbouri. Talk sparked questions and discussion afterwards

There was further discussion during a later session about my talk
Year(s) Of Engagement Activity 2011
 
Description Talk at Glasgow culture of care day on use of tissue engineered models to replace animals 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Matthew Dalby gave a talk on tissue engineering to help increase drug screening reproducibility
Year(s) Of Engagement Activity 2023
 
Description Talk at Glasgow haematology day 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Discussion around basic science models for use in haematology for which we need engagement of clinical practitioners.
Year(s) Of Engagement Activity 2023,2024
 
Description Talk in Portugal 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk for Dalby at University of Aviero
Year(s) Of Engagement Activity 2022
 
Description Thesis competition 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Professor Matthew Dalby on judging panel for lifETIME CDT 3-MT thesis competition.
Year(s) Of Engagement Activity 2023
 
Description UKSB 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation paper presentation
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Dr M. P. Tsimbouri. Interesting discussion following presentation

Discussion lead to problem solving for a fellow scientist
Year(s) Of Engagement Activity 2010