Nobel Prize-winning research lays foundations for cancer research at Apoptosis Research Centre, NUI Galway

This week, the 2016 Nobel Prize in Physiology or Medicine was announced and, much to the delight of cancer researchers working in the same field at the Apoptosis Research Centre in NUI Galway, it was awarded to Yoshinori Ohsumi for his discoveries of mechanisms for autophagy. Autophagy is a mechanism that our cells have for breaking down and recycling parts of the cell and Professor Ohsumi’s breakthough discoveries in the early 1990’s laid the foundations for autophagy research worldwide, including important cancer research at the Apoptosis Research Centre in Galway.

Professor Afshin Samali, Director of the Apoptosis Research Centre, and his colleagues are interested in finding out how our cells respond to stress (such as in cancer when a cell is required to rapidly grow and divide), and what tips the balance of whether a cell lives or dies in response to the stress.

Recently, Professor Samali’s group made a landmark discovery linking cell stress, cell part recycling (autophagy) and cell death, which has altered our understanding of how cells die and has relevance for how we treat cancer cells. Cancer cells often have defects in their cell death machinery that allows them to survive stress that would otherwise cause them to die. Professor Samali’s group found that when cells with defects in their standard death machinery are put under prolonged stress, autophagasomes, the cell’s recycling plants, provide a platform to activate an alternative cell death pathway (via caspase 8). This was the first time that this unique cell death-inducing complex was discovered, and Professor Samali’s group have termed it the ‘Stressosome’.

This research has important implications for cancer, as resistance to chemotherapy is a common problem in the treatment of cancer, and it is frequently caused by defects in the standard cell death machinery (mitochondrial death effector proteins). So, alternative stress-induced cell death pathways, such as the one discovered by Professor Samali’s group, may be particularly useful in tackling the problem of chemoresistance in cancer cells.

In addition to this landmark discovery, Professor Samali’s group have had other important findings in the area of cell stress and autophagy. For example, their research published earlier this year implicates a new protein, Sestrin 2, in controlling cell stress responses by activating autophagy. This research showed that that breast cancer cells ramp up production of SESTRIN 2 in order to dampen the cell’s stress response and survive harsh conditions.

Most recently, Professor Samali and his colleagues at the Apoptosis Research Centre, Dr Adrienne Gorman, Dr Eva Szegezdi and Dr Howard Fearnhead, have contributed to international guidelines on the use and interpretation of tests to monitor autophagy. These guidelines provide a benchmark to standardise the reporting of autophagy, an expanding field of research, across the globe.

According to Professor Samali, “the award of the 2016 Nobel Prize in this area acknowledges the incredible talent of Professor Ohsumi in his insightful, early experiments to uncover the intricate mechanisms of autophagy, and highlights the value of ongoing research in this field to human medicine. In particular, we at the Apoptosis Research Centre are proud to have contributed substantial knowledge to this field, which has direct relevance to cancer, and we too acknowledge that our work was built on the foundations laid by Professor Ohsumi.”

Research in the area of autophagy is ongoing at the Apoptosis Research Centre, with researchers Karolina Pakos-Zebrucka and Izabela Koryga investigating the steps involved in the assembly of the stressosome and identification of its molecular components.

Acknowledgements:

Professor Samali’s research is supported by funding from Breast Cancer Campaign grant (2010NovPR13), Health Research Board (grant number HRA-POR-2014-643), Belgium Grant (IAP 7/32), A Science Foundation Ireland (SFI) grant co-funded under the European Regional Development Fund (CÚRAM, grant Number 13/RC/2073) and EU H2020 MSCA ITN-675448 (TRAINERS).

Individual Researchers in Professor Samai’s group have been funded by an Irish Cancer Society Scholarship (CRS11CLE) and Thomas Crawford Hayes Funds of NUIG, Irish Research Council Employment Based Programme Scholarship Scheme

(EBPPG/2014/57, EBPPG/2014/74, EBPPG/2016/294), Irish Research Council Scholarship Scheme (GOIPG/2014/508, GOIPD/2014/53), and NUIG Hardiman Fellowship programme.

For further information/ original research articles, please see the following links:

Nobel Prize 2016 Press Release:

https://www.nobelprize.org/nobel_prizes/medicine/laureates/2016/press.html?ctkey=autophagy

Professor Samali’s research linking cell stress, autophagy and cell death, published in the journal ‘Autophagy’ in 2014: https://www.ncbi.nlm.nih.gov/pubmed/25470234

Professor Samali’s research linking cell stress and autophagy via SESTRIN 2: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914282/

Guidelines for use and interpretation of assays to monitor autophagy: https://www.ncbi.nlm.nih.gov/pubmed/26799652

Pictured are Apoptosis Research Centre Researchers that contributed to Professor Samali’s landmark autophagy findings: (L-R) Dr Svetlana Saveljeva, Karolina Pakos-Zebrucka, Dr Susan Logue and Professor Afshin Samali.

 

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