#IrishResearchCouncil – Blog about neuroblastoma research

How things work in science: Gene editing technology

Few advancements in biomedical sciences hold as much promise for revolutionising cancer research as CRISPR-Cas9. This ground-breaking gene-editing tool has sparked a wave of innovation, offering precision and efficiency in manipulating the human genome in the fight against cancer.

Now, what is it? CRISPR is basically an acronym for a very long name Clustered Regularly Interspaced Short Palindromic Repeats Associated Protein 9 or CRISPR-Cas9 for short. It was found in simple organisms such as archaea and bacteria. Interestingly, this is a component of bacterial immune systems that can cut DNA. So, this feature was proposed for use as a gene editing tool, a kind of precise pair of molecular scissors that can cut a target DNA sequence. So, the CRISPR-Cas9 scissors allow us to precisely edit the DNA sequence of living organisms by adding in (knock-in) or removing (knockout) a gene of interest.

For cancer research, for example, the CRISPR-Cas9 scissors can be used to introduce therapeutic genes or correct mutations associated with cancer predisposition syndromes. Meanwhile, those scissors can also disrupt genes involved in treatment resistance, sensitising cancer cells to existing therapies.

Jennifer Doudna and Emmanuelle Charpentier have won the 2020 Nobel Prize in Chemistry “for the development of a method for genome editing.”. A nice accompanying piece was published in The Conversation, highlighting the history of these scissors and the politics behind it.

Jennifer Doudna explains this revolutionary genetic engineering tool in a TED lecture. However, she warns:

“All of us have a huge responsibility to consider carefully both the unintended consequences as well as the intended impacts of a scientific breakthrough.”

I hope you enjoyed it!

Witten by Rabia Saleem

Congratulations to Dr Ciara Gallagher!

Huge congrats to a newly minted Dr Ciara Gallagher! She defended her PhD on March 8 – International Women’s Day. Your enthusiasm and perseverance are truly fascinating! May this be the stepping stone towards a brighter future, Ciara!

We thank examiners Dr Marie McIlroy (RCSI) and Prof Jan Škoda (Masaryk Uni) for the time and expertise they provided.

We also thank the Irish Research Council for their generous support!

Dr Ciara Murphy (Chair), Dr Olga Piskareva (Supervisor), Dr Ciara Gallagher, Prof Jan Skoda (examiner), Dr Marie McIlroy (Examiner)

How things work in Science: Classifiers

For our next little series introducing a different thing in science and how it works every week, I decided to focus on classifiers. With artificial intelligence becoming more and more prominent in our daily lives as of late, I thought this would be a good lead into the explicitly science-focused topics to come. So, what is a classifier? How does it work? And why does it matter?

At their core, classifiers are algorithms designed to categorize input data into predefined classes or categories. They learn patterns and relationships from labelled training data to make predictions on new, unseen data.

Once features are extracted, identified and quantified from labelled or annotated input data, mathematical models are employed for pattern recognition and predictions.

These models can range from simple decision trees to complex neural networks, each with its own strengths and weaknesses.

Training these models is an iterative process. That means to produce one good classifier, lots of classifiers were created in the process: Every time the pattern recognition is run, the annotated data is categorised by the classifier and compared to the annotation class. Prediction errors are corrected, and performance is optimised. This whole process is one iteration. How many iterations are required for a well-trained classifier varies widely and is largely dependent on the input data and application. For my tissue classifiers, it took up to 20,000 iterations.

Classifiers use these models to categorise unseen data into categories the user-defined at the start. In the figure, you can see my annotated histological slides from which the classifier extracted patterns to then classify the rest of the slide and entirely unseen slides into tumour (red), stroma (green) and background (blue) classes.

From identifying fraudulent transactions, filtering out junk mail, targeted advertising, and facial recognition to unlock your phone or diagnosing diseases, classifiers play a vital role in automating decision-making processes and driving advancements across a wide range of industries. Keep your eyes peeled, and you can find more classifiers in action all around you.

Written by Ronja Struck

Women in Science: Rosalind Franklin

On a blog post series of Women in Science by a Cancer Bioengineering lab, you didn’t think you were going to get around reading about Rosalind Franklin, did you? In recent years, she finally started to receive the acknowledgement she is owed, placing her all the way up there in terms of famous scientists with Marie Curie and Albert Einstein.

As mentioned by Ellen last week, there were only ever 13 women to win the Nobel Prize in Physiology or Medicine. But in 1962, it was erroneously bestowed upon three men for the scientific breakthrough of a woman. This blog post would just as well fit into a true crime in science series.

All down to misogyny and a single piece of evidence: Photograph 51, an X-ray crystallography of the structure of DNA viewed perpendicular to the DNA fibre axis, revealing the double helix structure.

You will likely all remember James Watson and Francis Crick from biology classes in school. You were probably taught that they figured out the structure of DNA.

But at the same time, they worked together in Cambridge, Franklin was working together with her PhD student Raymond Gosling at Kings College in London. Forced to work alongside Maurice Wilkins, who did not take well to her confident, goal-oriented ways, which led her to criticise her well-respected peers and dared to interrupt and correct them.

Leading to her downfall in the race with Watson and Crick was that Franklin complied with her understanding of scientific ethics, and rather than rushing to publish her findings, she sought to verify them and replicate the findings in Photograph 51.

Betrayed by her colleague Wilkins after ample tensions over the years. He passes her priceless finding to the competition, allowing Watson and Crick to model the double helix, publish a breakthrough paper and relegate her to a methods paper in the same issue of the nature journal.

Tragically, her young death at 37 from ovarian cancer prevented her from witnessing the Nobel Prize being awarded for discoveries in the molecular structure of DNA four years later. Which in 1962 was not to be awarded posthumously. Instead, her reputation for years was dominated by the more than unflattering recollections in James Watson’s biography. The book clued the public into the crimes the three men committed. All the while tarnishing Franklin’s name, portraying wildly misogynistic images and downplaying her indisputable contribution to science. Only after society as a whole changed its views on women and misogyny did perceptions of Rosalind Franklin and James Watson finally get corrected.

Today, Rosalind Franklin’s legacy stands as a symbol of tenacity, intellect, and an unyielding spirit that will inspire generations to come. It is about time that science books get rewritten to remind us that those are the virtues we should hold in high regard. Rather than the yearning for glory and a legacy that we see in the pressure to publish, the chase of impact factors never intended to rank journals and scientists but as a tool for librarians and the impossible climb through academia, forcing impossible expectations on principal investigators to take on endless students and responsibilities. Let’s take this opportunity to refocus and make sure it’s the pursuit of knowledge and answering questions that drive science forward that determine our decisions.

Written by Ronja Struck

Navigating Time and Tasks in the PhD Journey – The Struggles of Autonomy

Embarking on a PhD is an exhilarating endeavour. It offers the freedom to structure one’s own time. But this autonomy can be a double-edged sword; while providing a sense of flexibility and leisure, it also presents challenges in managing time effectively, prioritising tasks, and maintaining a productive schedule. In the context of a PhD, self-discipline and efficient planning quickly become the guiding stars of success.

The absence of rigid working hours requires a strong sense of self-motivation and discipline to stay on track. Without proper time management, it’s easy to fall into the trap of leisurely indulgence, neglecting the essential tasks and milestones that shape the PhD journey. Never before did I appreciate nagging parents, teachers or just people to which you could outsource motivation and feedback as easily. In a PhD, you’re on your own. You’re the only one who truly cares that what you’re working on is getting done. Done well and done at the right time. There is your supervisor, of course, and maybe collaborators. But it is not their job to stand behind you and say have you done this yet or that yet. They don’t see how much work you do or don’t do in a day. No one tells you to get off your arse when you’ve just stared at a blank screen for 20 minutes, and no one tells you to give it a rest when a simple problem turns out to be far more time-consuming and exhausting than expected because things still need to be kept moving. In the end, you can only rely on yourself to tell you whether you have worked enough or not. No one else knows. That can be extremely motivating and similarly defeating when you feel like you’ve done nothing but work for a couple of weeks and the results still aren’t there, so it seems like it doesn’t make a difference.

To conquer the time management challenge, prioritisation becomes paramount. As a PhD student, the spectrum of tasks can quickly seem overwhelming. Between different avenues and tasks that would progress your project, keeping up with writing, creating figures for adjacent projects, producing posters and presentations for conferences, writing blog posts, and making videos for funders and meetings, there always are more things to do in a day than could possibly be crammed in on the most productive of days. Figuring out how to manage urgency and importance becomes crucial to staying afloat. Identifying the most critical tasks and allocating time accordingly ensures progress and prevents the accumulation of unfinished work.

Maintaining a reasonable schedule becomes a balancing act. Especially when you pepper a couple of meetings in the very early morning because your collaborators are in a different time zone. And yet creating and adhering to a schedule is the foundation of effective time management. Despite the constant changes and different requirements, I find it helps immensely to establish a routine to cultivate discipline and maintains an easy overview over the week to allow myself to check what has been achieved and how long it took, so I can gauge how much more I need to do or whether I get to relax and leave half an hour early another day. It is crucial to strike a balance between focused research, data analysis, writing, and personal well-being. Regularly reassessing and readjusting the schedule as priorities shift guarantees that all aspects of the PhD journey receive the attention they deserve.

Navigating the realm of a PhD requires a delicate dance between self-motivation and effective time management. While the allure of autonomy can be tempting, the importance of prioritising tasks and maintaining a schedule cannot be understated. By striking a balance between work and personal well-being, the PhD journey can be transformed into a harmonious symphony of progress and achievement. Well, that’s the idea anyway.

As you embark on your own PhD adventure, you realise every day that time is a precious resource, and effective management is the compass that guides you toward success.

Written by Ronja Struck

So this is science..?

Had you told me before I started my PhD that I’d rushedly be writing a blog post on a bus in Bergamo, and it’s all part of my project, I certainly would have laughed and figured sure, maybe as a one-time exception if I find out something fascinating. But no, this is my second conference abroad this year, out of five in the past 4 months. My view on science and what is important to conduct good science has significantly changed since then, though. I have a ton of data from my secondment to Vilnius, but it is not all analysed yet. There are a number of decisions left to be made before my project becomes fully rounded and provides useful conclusions that I could share with people. But conferences serve another purpose. If everyone was only there to present their finished project, who would they present them to? At the current stage of my research, exchanging ideas, receiving feedback and seeing what others do helps immensely to provide perspective and both motivate me to do more and do better, inspire me to find new angles and also to relax and understand the bigger picture your project is a part, rather than getting bogged down by the day-to-day issues that so easily cloud your mind in everyday routine (as far as a PhD allows for routine…). In this way, conferences can shape a project, inform analyses and provide far more than an excuse to be out of the office.

Even more enjoyable are, of course, conferences when they’re held in such beautiful places! I’d never been to Barcelona or Milan. While I have no intention of making the cultural metropolises of Athlone and Limerick pale in comparison, it does feel different when adding an afternoon of sightseeing, includes a couple of centuries-old towns that look like they fell out of a fairy tale and churches built in the 13 hundreds in 20 degrees in March rather than freezing your fingers off after just an hour outside or seeing some trees and an old pub. I never thought science would facilitate me seeing the world, but I am delighted that it does. And while I never would have expected it before, I can now appreciate the value of presenting your project halfway to ensure that it’s the best it could have been when it’s done.

Presented my project at the European Association of Cancer Research Conference on National Pathology because I was awarded the Organisation of European Cancer Institutes (OECI) travel grant. So, I could enjoy some of the stunning views in Bergamo and even visit Milan.

Written by Ronja Struck

Work-Life Balance as a final year PhD student

Hi everyone,

If you haven’t met me before, my name is Ciara. I’m a final year PhD student in the Cancer Bio-engineering group. My research focuses on using a 3D model of neuroblastoma to uncover pathways that cause cancer cells to invade other parts of the body, in a process we term ‘metastatic spread’. As a whole, I really enjoy my research and have a keen interest in the topic, making it easy to stay motivated and driven. However, as a final-year student, my lab days can be long and labour-intensive; unfortunately, experiments can sometimes span the weekends. This makes work-life balance hard to achieve. I have come up with three effective strategies that help me manage my workload and still enjoy my PhD work while taking the necessary time to recuperate. I would love to share them with you.

Make a fun recipe – After a stressful day at work, plan a yummy dinner meal. While science experiments can fail, recipes only ever end with a delicious reward of a belly hug after a long day. Making a home-cooked meal helps me take my mind off the day’s stresses and fill myself with nutrients that keep my immune system strong. Check out some of the delicious recipes I’ve made so far.

2. Attend conferences. Conferences are a great way to meet researchers on the same journey as you. They can help keep you motivated and trigger new ideas for your own research. My most recent conference was in Athlone. While I enjoyed presenting my research and listening to talks, I also took some time to make new friends from other universities and explore the history of county Westmeath – for example, having a Guinness in the oldest bar in Ireland (they have a Guinness world record to prove it).

3. Plan a holiday to work towards – There is no better motivation to complete your work than jet-setting off to explore a new country. I aim to take a short science break every 4-6 months. My most recent one was to the snowy Italian mountains for a week of skiing. I came back with lots of fun memories and laughs, feeling ready to launch into another few months of hard work.

Ski hols 2023

Written by Ciara Gallagher

A February Full of Conferences

For a short month, we really made the most of February in the Cancer Bioengineering Group. We attended not one, but two conferences both outside of Dublin, with presentations from every member of the group and more great memories made.

At the end of 2022, I was lucky enough to be sent on a 3-month research secondment to the Institute for Bioengineering of Catalonia (IBEC) in Barcelona, so I was delighted to return in February for the Transdisciplinary Approaches in Neuroblastoma Therapy symposium. I got to present my work from my secondment in “Flash-poster” style, alongside other group members Ciara, Lin & Alysia. Ellen and Ronja also did a great job presenting a more extended cut of their research, and we got to see team lead Olga give a round-up of our group’s work as a whole.

Outside of the conference schedule, I was tasked with the role of Tour Guide because of my familiarity with the beautiful city of Barcelona. I led a group of 20+ researchers to a small bar in the Gothic Quarter for some well-deserved refreshments after a day of conferencing, brought my team to my favourite tapas restaurant for lunch (I still dream of the croquetas) and went on a lovely walk up Montjuic Hill to take in the views of Barcelona and reminisce on the 3 months I had spent there.

It felt as though the Ryanair flight had just touched down in Dublin when we started preparing for another conference – the Irish Association for Cancer Research (IACR) meeting, taking place in Athlone. With great memories from IACR 2022 in Cork, I prepared for the conference with great excitement – looking forward to both interesting science talks, and good craic with the gang of RCSI researchers attending the conference. I had a poster presentation for this, again focussing on the work I carried out on secondment in IBEC as well as some work at home in RCSI. I enjoyed my chats with the poster judges who gave some good insights on the work. Ellen and Lin had oral presentations at the conference so again I got to resume my role as the group Twitter mom, taking pictures and drafting tweets while the girls showcased their great research.

Each day when the conference was drawn to a close we set our sights on having a bit of fun with the other attendees. We enjoyed a pint of Guinness and some Trad music in the oldest bar in Ireland – Sean’s bar (they had the certificate to prove this). We made friends from outside RCSI including researchers from Queens University Belfast and Sales Representatives from various lab supply companies, had a good dance in the residents’ bar of our hotel and took over the dancefloor of a small local club. The gala dinner was lovely as always, and I’ll forever have fond memories of my lab group playing “Heads Up” to entertain ourselves in between courses. Finally, a highlight for me was being given a Highly Commended Poster Award at the dinner, such a nice acknowledgement to receive for my work and a lovely way to wrap up the last conference of my PhD.

Written by Catherine Murphy

Ronja’s Travel to Vilnius University and the National Pathology Centre

Ronja received a 3 months EACR Travel Fellowship to travel and learn new skills from RCSI Ireland to Vilnius University and the National Pathology Centre, Lithuania, between July and October 2022.

She reflected on her personal and professional experience in the EACR Cancer Researcher blog. Enjoy the reading!

Ronja PhD is supported by the Irish Research Council and the Conor Foley Neuroblastoma Cancer Research Foundation.

Congratulations Dr Frawley!

June 9th 2022 – A Big Day for Tom and me. This is the end of the 4th year PhD marathon. A long journey through scattered showers and sunny spells, gale winds and stormy snow with sunshine developing elsewhere, turning chilly under clear skies on some days with temperatures below/above zero. The full spectrum of emotions and hard work spiced up with the COVID19 restrictions’ uncertainty. All these together have moulded into a new high skilled researcher – Dr Thomas Frawley.

The PhD Viva and celebration, June 9th 2022

My greatest thanks to Tom’s examiners Profs Elena Aikawa (Harvard Medical School, USA) and Marc Devocelle (RCSI, Ireland)!!

This work would not be possible without the generous support from the Irish Research Council and National Children’s Research Centre.