Secondments are the key mechanism driving bi-directional knowledge transfer in INSPIRED, are essential for reaching the research objectives, are beneficial for all parties involved and, importantly, will build collaborative networks that will last long into the future.
Benjamin Suarez, a PhD student from Prof. Afshin Samali’s lab in NUI Galway went on secondment to eNiOS in Athens, Greece.
I have been developing my skills as a researcher in the Apoptosis Research Centre in Ireland, with prof. Afshin Samali and Dr. Adrienne Gorman. At our laboratory in Ireland, we focus on delineating the unfolded protein response and its role in cancer, with the aim of bringing these discoveries to the clinic. I have focused my work on the role of IRE1 activity and finding a genetic signature which could be used to stratify cancer patients.
I went on secondment to eNiOS in Athens, Greece to work with prof. Aristotelis Chatziioannou's team of bioinformaticians. There, I learned many skills which I could apply towards making a gene signature.
I received training in the R programming language and its application in high throughput technologies, such as microarray and RNAseq. I was able to build an automated work flow for processing high-throughput data and obtained meaningful results.
Greece was a great experience, both for my training and for getting a taste of life outside of Ireland. The Athenians speak Greek, but many can speak English, especially the youth. I learned enough Greek to order food and manage the public transport. The museums are fully discounted for students, and I was also able to enjoy souvlaki everyday. Many of the locals go find work abroad, and were pleasantly surprised when I told them I was in Athens to work. Many expressed pride learning their home had something to offer me, especially in the field of cancer research.
Eoghan McGrath, a PhD student from Prof. Afshin Samali’s lab in NUI Galway is on secondment at Prof. Claudio Hetz’s lab at the University of Chile, Santiago
Prof. Samali’s lab in NUI Galway is focussed on understanding basic UPR biology and how we can translate this knowledge to clinical applications. Within Prof. Samali’s group is the UPR and Cancer team. As part of this team I have focussed on understanding the role of the IRE1 RNase domain in breast cancer, a disease which kills fifty-thousand people annually in the USA alone. With cancer incidence set to increase, understanding the molecular mechanisms underlying oncogenesis, metastasis, and therapy resistance in breast cancer are more important than ever.
In vivo studies provide crucial therapeutically relevant information on the effectiveness of different therapeutics in the treatment of cancer. Since the immune system is known to play many pro- and anti-tumour roles, syngeneic mouse models are superior to xenografts in providing clinically relevant results. To date, the effect of pharmacological inhibition of IRE1 RNase on tumour growth in immune-competent mice has not been evaluated. My secondment in Chile will allow me to address this large gap in our knowledge.
I have received training in the handling of mice, and the administration of different treatments from experienced researchers in the Hetz lab. Furthermore I have successfully completed an internal Animal Handling and Ethics course in the University of Santiago, Chile. This invaluable training has armed me with the relevant practical and ethical training to design and perform animal studies safely and with minimal distress to the animals. In addition to in vivo work, I have received training in a variety of other lab techniques. The most interesting of these has been the disaggregation and culture of cells from primary human tumours.
Outside of the lab, I did not experience as much of a culture shock as I expected. Chileans are relaxed, friendly and helpful. There is always a party to go to, or some new bar to try out. Like the people, Chile’s landscapes are diverse and beautiful. See if you can spot the Irish person in the photo from a recent trip I made to Patagonia.
This biggest hurdle I faced when arriving in Chile (besides negotiating the Santiago metro) was the language. I learned upon my arrival that Chilean Spanish is very different to Castellano (Spain Spanish) which I had been learning, and that trying to learn Spanish in Chile would be like a Chilean trying to learn English in Kerry. I am slowly improving my Chileano however, and have a newfound gratitude that science is communicated through English.
My experience in Chile has been great so far, and I am excited about what I will learn and achieve before the end of my secondment.
Dr. Alexis Rivas, an experienced researcher from the University of Chile is currently on secondment at NUI Galway, Ireland
In Dr. Claudio Hetz’s lab in the Universidad de Chile we study cellular processes that control protein synthesis and quality control in the endoplasmic reticulum (ER). We are particularly interested in how these processes are related to brain diseases such as Alzheimer`s disease, Parkinson`s disease, Huntington`s disease and amyotrophic lateral sclerosis, which are collectively known as protein misfolding diseases. Protein aggregation in the brain is a pathological event observed in all these diseases. Protein aggregates accumulate in the form of small oligomers, protofibrils, and large inclusions, and cause chronic alterations to cellular homeostasis triggering neurodegeneration and neuronal loss. Recent evidence indicates that the unfolded protein response (UPR) is constitutively activated in neurodegenerative diseases and that the modulation of the UPR network can reduce the formation of these protein aggregates, delaying disease symptoms. Therefore the UPR could potentially be a good target for therapeutic strategies.
As an experienced researcher I have expertise in developing cellular assays to detect and quantify intracellular protein aggregates. During my secondment to NUIG I will use these assays for high throughput screening (HTS) to identify compounds or extracts that can reduce toxic protein aggregates. My participation in the INSPIRED project aims to screen for new compounds or extracts from natural sources that can reduce the amount and/or size of the toxic protein aggregates. I am screening four libraries:
- the first has 40 synthetic compounds described as inhibitors of kinases, specifically IRE1a and PERK (branches or UPR);
- the second is a library of 1280 pharmacologically active compounds with neuroprotective properties associated with reduction of toxic protein aggregates.
- The third library is composed of natural extracts from Chilean native plants, highly rich in antioxidant components, which has been extensively linked to the reduction of ER stress and therefore could potentially have some components that can modulate one or more branches or UPR.
- The fourth library is composed or Irish marine microorganism extracts (algae, sponges, etc..). There currently is little evidence of marine-derived compounds modulating ER stress so this the most explorative library but has the potential to find new chemical entities with no intellectual properties assigned.
The four libraries are being screened in two assays of protein aggregation – one is based on a polyglutamine GFP-tagged aggregation-prone protein related to Huntington`s disease and the second is based on a polydipeptide GFP-tagged aggregation-prone protein related to Amyotrophic lateral sclerosis. Hits will be validated in neuronal models of transient expression of the protein of interest and finally in primary cultures and animal models of neurodegenerative diseases.
I am currently receiving training in drug discovery and HTS and availing of the expertise at NUIG to develop new cellular-based assays to evaluate whether modulation of one or more branches of the UPR could modulate the number of toxic aggregates in neuronal cells. During this secondment, I have attended a Drug discovery course (Frankfurt, Germany) and a Screening Chemical compounds course (Galway, Ireland) and I have started collaborations with the Fraunhofer Institute (Germany) who are highly experienced in screening campaigns and equipped with lastest technology.
Dr. Sandra Healy, a project manager at NUI Galway, went on a 1 month secondment to MannKind Corp in California, USA.
Sandra is an experienced scientist, program manager and grant writer. The goal of her secondment was to understand Mannkinds current activities and future plans for the development of IRE1 inhibitors as therapeutic agents. This knowledge will enable her to suggest ways that the academic collaborators in INSPIRED can take advantage of Mankind’s activities to increase understanding of IRE1 biology and biomarker development. This secondment will allow her to assess the potential opportunities for further collaborative work between Mannkind and academic partners and her secondment will strengthen the interaction between NUIGalway and the IRE1 team at Mannkind and facilitate the development of new US-EU collaborations on drug discovery.
Dr. Katarzyna Mnich from NUI Galway, Ireland went on secondment to MetaSysx in Potsdam, Germany to interact with the team and learn about their expertise and methodologies in metabolomics.
Dr. Katarzyna Mnich, a postdoctoral researcher at NUI Galway, went on secondment to MetaSysx in Potsdam, Germany . Katarzyna is an experienced molecular and cellular biologist and has worked extensively on the Endoplasmic Reticulum stress response and on the role that IRE1 plays in this response. Katarzyna remained at MetaSysx for 3 months where and learned how to use MetaSysX’s platforms to analyse of the impact of modulating IRE1 on lipid metabolism. The data can be used by academic collaborators in INSPIRED to increase our understanding of IRE1 in cancer biology. While on secondment at MetasysX Katarzyna obtained multilevel training including metabolomic technologies and methodologies, metabolite annotation, high throughput data analysis, pathway mapping, project and team management.
On return to NUI Galway, Katarzyna brought new knowledge and skills that she will disseminate to enhance the capabilities of her home institution. We look forward for a further successful collaborative work with MetaSysX!