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lifeTIME CDT Newsletter February 2022

CDT Students

lifETIME CDT Students - Photo courtesy of Ibrahim Erbay (NUI Galway)

We now have 52 fantastic students across our three cohorts and we are excited to continue to grow further as we recruit our 4th cohort later in the year.

This year will see our third-year students (2019 cohort) exploring their career aspirations as they undertake a placement with our industry and charity partners. Third-year students will also take the lead on organising our joint CDT conferences that will take place this year.

Our 2020 cohort are now making great progress with their research as they push full steam ahead into the second year of their PhD. This year the students will be trained on the importance of data quality in analytical science and understand the activities undertaken in laboratories to ensure the reliability of measurement. This training will be provided by our partner company LGC Standards. The students will complete Entrepreneur Business School training and learn more about IP and the freedom to operate within their field. We are also excited and very much look forward to watching the students' short 60 second film showcasing their research to the wider community.

Our first-year students (2021 cohort) have already had a great start to their training, made easier by the fact that they could come together in person from the outset and got to enjoy three full weeks together across each university location. This year the students will have the opportunity to meet a wide range of our partners during our career series and attend their first retreat where they will complete Responsible Research and Innovation training.

New Student representatives

Congratulations to the newly appointed 2021 student representatives. Our student representatives work as a liaison between the student body and the CDT management team to help us improve and refine the CDT.

  • Executive Management Committee - Amaziah Alipio (University of Birmingham)
  • Interdisciplinary Skills Committee - Juda Milvidaite (University of Glasgow)
  • Equality, Diversity, and Inclusion Group - Lola Ajayi (University of Glasgow)
  • Skills and Training Committee - Elaine Duncan (University of Glasgow)
  • Sustainability Working Group - Adam Efrat (Aston University)
Student Voice - 2021 Cohort

Review Papers

Modelling the central nervous system: tissue engineering of the cellular microenvironment

Paige Walczak (Aston University) discusses her recent co-written review paper:

Due to an ageing population and a distinct lack of treatments, neurodegenerative diseases such as dementia are becoming increasingly common. Traditionally, animal testing has been used to explore potential treatments, but this is unethical and not actually that comparable to humans. Creating artificial tissues in the lab allows us to better understand how the human body works in health and disease! By modelling neural tissue like the brain, we can test therapeutic drugs for dementia faster and more efficiently.

My review outlines current approaches for modelling brain tissue, highlighting the pros and cons of in vitro (“grown in the lab”) techniques. Within the field of neural tissue engineering, organoids, bioprinting and biomaterials are particularly popular, with gel-like materials able to recreate the unusual mechanical properties of the brain. By fine-tuning mechanical properties such as stiffness, the final model will better represent living tissues seen in humans! The review also emphasizes that the future of tissue engineering relies on development of next generation biomaterials and techniques, capable of producing cutting-edge dynamic constructs with a high level of detail e.g. microscale stiffness changes to promote specific cell types!

This ties in nicely to my project within the lifETIME CDT, where I look to engineer artificial neuronal networks in 3D in order to create an in vitro system capable of modelling the Cortex. Specifically, methods of modifying hydrogel biomaterials for improved functionality is my current focus.

Hydrogels: 3D Drug Delivery Systems for Nanoparticles and Extracellular Vesicles

Yashna Chabria (NUI Galway) discusses a recent co-written review paper:

Nano-sized therapeutics such as synthetic nanoparticles (NPs) and extracellular vesicles (EVs) have emerged as versatile vehicles for the delivery of therapeutic cargo in a range of clinical settings. Their small size and modifiable physicochemical properties support refinement of targeting capabilities, immune impact, and therapeutic cargo, but rapid clearance from the body and limited efficacy remains a major challenge. This limitation highlights the urgent requirement for a local sustained delivery system for NPs and EVs at the target site that will ensure prolonged exposure, maximum efficacy and dose, and minimal toxicity.

Biocompatible hydrogels loaded with therapeutic NPs/EVs hold immense promise as cell-free sustained and targeted delivery systems in a range of disease settings. These bioscaffolds ensure retention of the nano-sized particles at the target site and can also act as controlled release systems for therapeutics over a prolonged period of time. The encapsulation of stimuli sensitive components into hydrogels supports the release of the content on-demand.

This review focusses on the sustained and prolonged delivery of these nano-sized therapeutic entities from hydrogels for broad applications spanning tissue regeneration and cancer treatment. Further understanding of the parameters controlling the release rate of these particles and efficient transfer of cargo to target cells will be fundamental to success.

My PhD is focused on developing a dynamic, clinically relevant model of breast cancer to study trafficking of therapeutic EVs towards breast tumours and lymph node metastases in vitro. The EVs will be incorporated into a hydrogel in order to facilitate sustained release and subsequent uptake by breast tumours and lymph node metastases, potentially supporting prolonged therapy in patients with advanced disease. The dynamic multi-organ set up will allow me to interrogate interactions between the primary tumour and lymph node cells that occurs in breast cancer patients when the disease starts to spread. Development of this system aims to minimize the use of animal models. This will support improved understanding of breast cancer metastasis and allow us to harness this knowledge to develop a novel treatment for patients with advanced breast cancer.

Microfluidics as a Novel Technique for Tuberculosis: From Diagnostics to Drug Discovery

This review article covers the use of microfluidic technology for tuberculosis (TB) diagnostics, drug discovery and research methods. TB is the second leading infectious killer since the global COVID-19 pandemic. Despite most TB strains being treatable with antibiotics, some of the key medical challenges include achieving rapid diagnostics, the rise of multidrug-resistant TB, and the poor treatment efficacy of latent TB.

The article gives a comprehensive explanation of how microfluidics works and describes different studies which have applied this novel technique to TB diagnostics and drug discovery. We have found that throughout the literature, microfluidics has extensively been used in tuberculosis diagnostics and there is a gap in the field for using this technology for drug discovery. There is scope for creating a more physiologically relevant in vitro model and carry out antibiotic susceptibility testing in a standardised and high-throughput manner

Written by co-author Antiona Molloy (Aston University).

Resident Macrophages and Their Potential in Cardiac Tissue Engineering

Within the world of biomedical engineering, tissue engineering is one of the most exciting avenues of research today. Researchers in this field are utilizing the insights of physiology and a those of material sciences to examine cellular mechanisms of both healthy and diseased or damaged tissues, to generate models for testing novel treatments, and to create new tools for the improvement of regenerative medicine.

Since the late 20th century, researchers have been utilizing technological advancements to generate ever more complex tissues in vitro, giving rise to a great deal of interest in the area. One tissue of particular interest is, of course, the human heart, with multiple cell types working in synchrony to pump an unfailing supply of blood around the body. Hence, generating an effective model of the heart is challenging. However, if a model of this organ could be generated in the lab, its impact could lead to fundamental changes to how we treat and care for heart conditions. In order to achieve this goal, we need to understand the roles played by different cell types in the heart. Recent studies have shown that immune cells, specifically macrophages, are very important for the normal functioning of the heart. The review by Suku et al. (https://www.liebertpub.com/doi/10.1089/ten.teb.2021.0036) explores the potential of using macrophages as an additional cell source to engineer cardiac tissues.

Macrophages are specialized immune cells found in all vertebrates and are an essential player in both defense and normal function. Our understanding of macrophages has evolved greatly from their first discovery, initially perceived as cells that only respond to microbes, we now know they act as key mediators of tissue homeostasis. Macrophages were once believed to originate from the bone-marrow alone, but we have come to realize that they can also be embryonic in origin; this type being commonly referred to as ‘tissue resident’ macrophages. Tissue resident macrophages remain in their host tissue and maintain homeostasis within tissues. Some common examples include microglia, Kupfer cells, alveolar macrophages, and cardiac resident macrophages. Although only present as a small population within the heart, cardiac resident macrophages ensure normal heart function by performing phagocytosis, facilitating electrical conduction, promoting regeneration, and removing cardiac exophers. However, most of the recent studies involving engineered heart tissues (EHTs) focus only on the interplay between cardiomyocytes and cardiac fibroblasts. As a heart without macrophages would not function, it is essential to include a resident macrophage population in the EHTs, to improve their functionality and make them more physiologically relevant. Additionally, since obtaining healthy cardiac resident macrophages in vitro is challenging, Suku et al. discuss potential ways to achieve this. By building on our strong foundational knowledge on different macrophage populations and with the assistance of new technologies, we will hopefully see rapid progress in finding new therapeutics using cardiac tissue engineering.

Written by Meena Suku (Trinity College Dublin)

Student Placement

ANIMAL FREE RESEARCH UK

Narina Bileckaja (University of Glasgow) has just returned from a 6-week scientific communication placement with Animal Free Research UK. Narina talks below about her placement experience:

As an early career researcher, I tend to evaluate the quality of my work by tracking how many experiments I carried out and the amount and quality of data I acquired. However, I recently started considering that the general public’s opinion about science and research might be. I realised that it can sometimes prove hard to find information about research explained in a way that is understandable for everyone, independent of their background. Not only that, but research results can also be cloaked in mysterious scientific terms that can only be understood by other scientists working in the same research field.

As for why I got interested in this topic to begin with, a lot of lifETIME CDT projects are focused on new advanced technologies that allow researchers to carry out human-relevant studies. My PhD project is no exception; thus, I came to realise the importance of the ability to explain the work we do in such a way, that more people learn how interesting and important it is, and how it will improve people’s lives. Hence, I decided to do a placement with a company or charity that has science communications at its heart.

I could not have found a better place than the Animal Free Research UK (AFR-UK) charity. As AFR-UK communicate with both the public and the scientific community, I got a chance to see how the communication style changes depending on the target audience. During my placement with AFR-UK I learnt how crucial the wording and the tone of every written piece is for conveying the message in a clear and understandable way. I also learnt how important it is to always keep in mind who you are writing for, and what your audience is interested in.

The science communication placement with AFR-UK made me appreciate, more than ever, the importance of clear and inclusive writing in scientific communications. As a scientist, I focus on data and experiments, but at the end of the day the research I do should be one of the steppingstones on the way to improving research and healthcare. So why not talk about the exciting, life-changing science in a way that is interesting and engaging for as many people as possible?

WOMEN IN ENGINEERING SCIENCE AND TECHNOLOGY (WEST) SOCIETY

The Chair of the WEST Society at Aston University: Paige Walczak, discusses her new role within the Society and why it is important to her.

The latest UCAS data from HESA shows only 35% of STEM students are female, with these numbers dropping even further when we look at women in STEM workplaces. It is not enough to notice the numbers and contemplate why this might be. I believe something must be done to tackle the invisible barriers women in STEM face. That is why I ran for Chair of the Women in Engineering Science and Technology (WEST) society at Aston. Fortunately my peer and friend Megan Boseley supports me as Vice-Chair, allowing us to provide additional insight from a postgraduate perspective into the society.

Thanks to WESTs’ founder Gabriella Gardosi, for over 4 years we have been engineering a more inclusive environment for women in STEM. Our core missions include promoting careers & placement options, reaching out to young girls within the wider community and supporting women at Aston! As chair of the society I have pushed for greater exposure of our students to successful women in academia & industry, after all ‘you can’t be what you can’t see’. This year we also aim to collaborate with other societies for a series of events during international women’s week; including a self defence class, sponsored sport event for charity and a networking day.

Ultimately WEST aims to empower young women studying STEM subjects and beyond!

I-GENE Summer School

Maria Laura Vieri (University of Glasgow) attended the Nanomedicine for Gene Therapy (I-Gene) Summer School. Maria Laura talks about her experience below:

My PhD focuses on the development of a hydrogel-based 3D model of the cartilage for arthritis research, using human induced pluripotent stem cells (iPSCs) as cell source. Apart from the interest in joining the engineering field, one of the reasons why I decided to apply for this project was the possibility to work with iPSCs and genetically modify them using the well-known CRISPR-Cas system.

Given my interest in genome editing, I decided to apply for the summer school “Nanomedicine for Gene Therapy”, held by the I-GENE scientists in Pisa (Italy), during the summer of 2021: the program included 3 days of online training, with lectures and virtual labs, and an additional day covering the ethical and legal issues of gene therapy and genome editing. This event caught my attention not only due to its exceptional speakers, but also for the possibility to attend practical sessions that enriched my knowledge in model systems for genome editing and nanoformulations (topics I already covered during my master’s degree).

Lectures started with a general overview on genome editing, the CRISPR-Cas system, nanomedicine and gene therapy, including challenges and limitations. This session also included a detailed virtual lab experience on the use of zebrafish as model system. The speakers also offered an introduction on nanophotonics, with an insight on their employment for gene therapy, and a fascinating practical session on nanoformulation synthesis and characterisation. After the roundtable on ethics and legal issues of genome editing, the event concluded with an exciting talk on the I-GENE project (https://i-geneproject.eu/), funded by the European Commission. At the heart of this project there is the concept of “programmable nanomedicine”, a stimuli-responsive nanoformulation that allows for a precise single cell editing, with both temporal and spatial control on its activation. This technology, that aims to increase the safety of genome editing and expand its clinical applications, already has proof of concept results in zebrafish and will be further validated in a murine model of melanoma.

Despite being held virtually due to COVID restrictions, this summer school has been a fascinating, interactive and well-organized event. I highly recommend it to all those interested in genome editing and gene therapy.

Stakeholder Day

The event will take place on Tuesday 8th March 2022 at the University of Glasgow, University Union, Debating Chamber.

The stakeholder day will bring together lifETIME students, academics, industry partners, iClub members and steering group. The purpose of the event is to capture our stakeholder views form which the management will use to refine the CDTs impact strategy.

There will also be an opportunity for all attendees to network at the conference dinner. If you wish to attend, please make sure you select the conference dinner ticket when registering. We look forward to seeing you at the event.