The first month of the new year and the first challenge. Monday is the big day for me. In the essence, my grant application was shortlisted for the interview where I have to face the challenge and prove that I worth it.
The proposed application seeks to go to the US lab and gain an expertise in an interdisciplinary methodology to monitor and capture the dynamic of cancer spread (metastasis) in real time. This experimental approach would accelerate our understanding of neuroblastoma metastasis which is one of the reasons for failure in the treatment of neuroblastoma. If we know how neuroblastoma cells spread, then we can find the weaknesses in the process and create new drugs or use existing to target it.
I feel that sharing my worries with you makes me stronger. I am looking forward to this challenge with my head up and hope to feel your support at this crucial moment.
When I look back on my journey in 2017, there were many junctions, traffic lights and stops as well as ups and downs. Junctions were to make decisions, while traffic lights and stops – to be patient. Ups and downs were my feelings of satisfaction. The good mix of both kept me to stay human. It is not the number of grants received that matters it is who around you. I have met genuinely curiosity-driven students who made this journey fascinating and very special.
My most memorable Ups were the successful examination and graduation of my PhD student John Nolan, organisation and chairing the IACR Meeting session: Challenges in Childhood Cancers, the Mad Hatter’s Tea Party and the Gala Dinner with the CFNCRF, the launch of my very own research team thanks to the funding by the NCRC and the Neuroblastoma UK, the successful completion of two final year undergraduate and two MSc projects, and welcoming the new PhD student Tom Frawley.
My team is growing and I am looking forward to 2018!
The researcher’s path includes days when you feel so low because your grant or paper was rejected or even both within a very short time frame. It happened to me a couple of weeks ago. At this point, I felt helpless sarcastic and non-motivative reading reviewer’s comments. One reviewer mixed up neuroblastoma with a brain tumour, so their comments were not relevant. Another just found no time to read through, the sentence was very short – ‘not a priority or interest‘. One more went to their area of expertise asking to fulfil it rather than comment on the actual focus of the study. Such comments are so common that any submission of results or a proposal could be considered as a draw. It has been neither my first time not the last. More to come.
As a part of Science Week, our Department hosted Lab Safari for the secondary school students aiming to give a sense of what scientists do in the lab. The focus of my research is the identification of novel biomarkers for neuroblastoma response to chemotherapy. So, we decided to explain the concept of biomarkers and the importance of discovering novel biomarkers for neuroblastoma. Between me and John we covered biomarker’s basics and carried out the detection of MYCN in neuroblastoma cell lines. Here, I am summing up our activities in the form of Qs & As:
1. What are biomarkers?
Biomarkers are signposts of the body condition. Biomarkers – bio is for biological and markers – for molecules indicating that something is going wrong or differently in the body. They can help doctors to read these changes and identify a condition or disease. There are biomarkers for heart disease, cancer, diabetes and many others.
2. What type of molecules can serve as biomarkers?
Various types of molecules can do the job as long as they can differentiate the normal and abnormal process in the body. It can be DNA, RNA, proteins and hormones. These molecules can be detected in the blood, urine, stool, tumour tissue or any other bodily tissues or fluids.
3. How can we discover novel biomarkers?
Research, research and again research. We have to learn more basic facts about DNA, RNA and proteins. We need to be able to link this knowledge with health conditions including cancer. We need to identify how these molecules speak about the unhealthy conditions. We need to explore whether biomarkers exist within the disease that can predict the response to treatment and outlook.
4. What biomarkers are known in neuroblastoma?
There are various biomarkers that are specific for neuroblastoma. Catecholamines in urine are chemicals produced by neuroblastoma cells. Chromogranin A – is a protein that can be detected in the blood. It is unspecific biomarker because it can be secreted by neuroblastomas and some other tumours (e.g. pancreas and prostate cancer). Various chromosomal aberrations can be biomarkers of neuroblastoma aggressiveness. One of the strongest predictors of rapid neuroblastoma progression is MYCN status.
5. What is MYCN?
The MYCN is a proto-oncogene protein and a member of the MYC family of transcription factors. MYCN was identified in 1983 and very soon became a routine biomarker for neuroblastoma aggressiveness. This protein is very important for the normal embryo development. The amplification of this gene leads to the excess of MYCN protein in cells prompting cells to grow and divide faster transforming normal cells into tumour cells.
6. How did we detect MYCN in neuroblastoma cell lines?
A day before the demonstration, we carried out some preparation steps. We selected several neuroblastoma cell lines with known MYCN status. Some cell lines had MYCN amplification, other didn’t. Among those that did have the amplification, the expression of MYCN protein was different giving us a good illustration of biomarker’s quantity. So, we run SDS-PAGE, a technique that helps to separate the cellular protein mix based on their size.
Then the separated proteins were transferred onto a membrane and exposed to a buffer containing an antibody for MYCN (primary antibody). This antibody recognises only MYCN. At the next step, we added another antibody that has a dual role – it can attach to the primary antibody and produce a signal that can be visualised. The next step would have been the visualisation itself and the one for Lab Safari. So, we were ready.
Once we finished the basics of biomarkers, we moved to the biomarker MYCN detection step. The buffer for visualisation was added and the membrane was imaged.
If you like this idea and want to have this demonstration for your science classes at school, please contact me and we would be happy to do it for you.
#ChildhoodCancerAwarenessMonth is over. However, childhood cancer is not going away. The battle is not over. Families will be still affected by the lack of treatment options available to their child. More research is needed. Please do support enthusiastic people who do want to make the change. Every single contribution counts.
The more important reason is that the research itself provides an important long-run perspective on the issues that we face on a day-to-day basis. (Ben Bernanke)
I would like to thank everyone who followed my blog during this month and hope would continue!
We hear great news from the US labs that a new treatment is on the way for children with cancer. Most of their research is funded by charities and success stories appear because of the people who want to make dreams come true for kids with cancer and their families. Dreams for longer and healthier life.
Interestingly, the study led by Professor Bernie Hannigan, the University of Ulster, which was published by Medical Research Charities Group, identified main gaps that keep Ireland at the bay:
Childhood cancer research areas are not prioritised, including neuroblastoma.
No Government funding support for childhood cancer research. The research has to compete on general terms with well-funded research groups/centres/clusters focused on the adult cancers (breast, prostate, etc)
No systematic involvement in research of Patients or other lay people.
No medical research charities to fill the gap in childhood cancer research funding.
Dedicating posts to neuroblastoma and childhood cancer awareness month, it is impossible to stay distant about the need of fundraising to fund research. The #ChildhoodCancerAwareness Campaign aims not only attract our attention to the fact that kids get cancer too, but mostly to show how little is done to understand the causes of the disease and offer effective treatments.
To address the last problems more research is needed both curiosity-driven and translationally focused. To answer the question why research needs more funding, in general, you can find here.
Effective treatments cost money: only 4% of research funding goes to research in ALL childhood health conditions. In the other words, every 4cents of each 1 euro are to be used in research.
The causes of childhood cancer including neuroblastoma are not known. It would be right to expect more blind alleys and failed ideas in the understanding these cancers.
The research can take decades, so it is a long-term investment. In contrary, people, who can give money (the politicians and governments), have 4-5 years of political power. 4-5 yearsvsdecades = the discovery research becomes critically underfunded.
Walking in Mainz last week I saw a lovely fountain capturing 3 girls under umbrellas (Drei-Mädchen-Brunnen) at the ball square. This fountain was built between two Catholic girl’s schools symbolising the separate education and happy childhood. It has charmed me and reminded rainy days in Ireland and how this fountain may fit any park or square in Dublin.
My second look at the picture gave me another perspective. This sculpture could illustrate not only happy childhood but also the protection we can give to children with cancer being their umbrellas. As September is childhood cancer awareness month, I am picking this picture to support this call. Raising awareness about childhood cancer we help to make their dreams come true. Dreams for better treatment, better quality of life full of love ahead through better funding of childhood cancer research and access to innovative treatments.
The focus of the scientific program was on “Translating Science into Survival”. Talks covered the challenging areas in cancer immunology and immunotherapy. The full list of topics can be found in the meeting program.
At the moment cancer immunology and immunotherapy is a hot topic in the next generation of anti-cancer therapies. Lots of attention is given to checkpoint immunodrugs as it was proven by the prevalence of talks on this subject in the program. Indeed, this drug has great potential, but at the same time, it is not universal. About 50% of patients do not benefit from it.
What lessons have been learned from the talks:
Checkpoint immunotherapies are the main stream
Not all cancer patients would respond to immunodrug
Genetic landscape of a tumour and/or the patient may contribute to this, thus making beneficial to check genetics for this type of treatment
Immunodrugs work better in combination with conventional therapies such as chemotherapy.
The immune system can be tuned by a drug, but it will switch on compensatory mechanisms to balance the intervention.