How the NICB is working with industry partner Alltech to tackle sustainable food production
The world population is projected to increase to 9.7bn by 2050, placing increasing demands on food production. To meet this requirement, agricultural and animal health industries need to develop innovative solutions for sustainable food production, while considering animal wellbeing, energy and resource limitations. Trace minerals such as copper, iron, selenium and zinc are essential in the diet but both deficiency and over exposure can both result in deleterious consequences and can be detrimental to health (for example immune function impairment). Much has yet to be learned regarding uptake and processing these minerals, especially at the primary site of absorption: the intestinal epithelium.
To address this challenge as an opportunity, the National Institute for Cellular Biotechnology and Alltech Ireland have formed a partnership to develop models which allow us to examine how intestinal cells process trace minerals. Have a look at the video below for more information:
The NICB-Alltech partnership proposal was initiated with the primary goal to achieve a greater understanding of the regulation of mineral levels, the impact of manipulating these levels in mammalian tissues and whether this is influenced by the type of mineral, a study referred to as nutrigenomics. Our mission is to develop and optimise a number of in vitro cell models which track changes related to micronutrient exposure, for minerals in isolation and combination, incorporating genetic and proteomic analysis following uptake and transport of the micronutrients. Current focus is on the impact of inorganic and organic trace minerals on cellular health and function.
Key members of the project are Professor Martin Clynes (head of the DCU research team), Dr. Richard Murphy, the Director of Research at Alltech and Associate Research Director, Dr. Karina Horgan. The DCU team includes Dr. Finbarr O’Sullivan (Associate Director of the NICB) and Dr. Joanne Keenan (Research Fellow), and two PhD students, Ali Coyle and Charles O’Doherty (author). Other members of the NICB-Alltech team include Dr. Niall Barron, Dr. Paula Meleady, Dr. Padraig Doolan and Mr. Michael Henry.
In his role as research director Dr. Murphy is currently involved in multiple areas including peptide bio-marker detection, nutrigenomics, antimicrobial resistance and regulation of protein production. Dr. Horgan is currently responsible for Alltech Life Sciences research in Europe and as part of this she has formed a cellular biology research group focused on developing cellular-based bioactivity assays and profiling yeast products.
My research background is in cell biology, having completed a four year biotechnology degree in DCU in 2011 and working in various roles in the pharmaceutical and orthopaedic industries in the years prior to securing my PhD studentship. While I enjoyed my experience in these positions, I knew my academic life was not over yet.
I began searching for research positions combining my primary interests: cell culture and nutrition. I was fortunate enough to find and secure one in both these interests, at the NICB in DCU. I am currently doing a Ph.D. along with my colleague Ali Coyle (supported by Alltech Ltd. and Enterprise Ireland) under the mentorship of Dr. Keenan and Dr. O’Sullivan.
Left: Members of DCU team; Ali Coyle, Charles O’Doherty, Dr. Finbarr O’Sullivan and Dr Joanne Keenan
Right: Director of Research for Alltech, Dr Richard Murphy presenting at the business matchmaker event on 11th May in the Helix, DCU
Cellular conditions within the small intestine are critical for health and performance in humans and animals, due to its crucial role in controlling uptake of essential minerals and nutrients and protecting the body from pathogenic organisms. This is evidenced by genetic mutations related to intestinal nutrient uptake such as the debilitating disorders: Menkes disease for copper and hemochromatosis for iron. Our team use a multi-targeted approach to assess interactions between micronutrients and the intestinal epithelium, such as mineral micronutrient competition, toxicity, transport and uptake.
When conducting in vitro intestinal studies, Caco-2 cells are differentiated over a 21-day period on permeable supports to generate enterocyte-like cells that mimic the small intestine. Confirmation of differentiation is established by Western blotting for markers of mature enterocytes (e.g. Sucrase isomaltase) and confocal microscopy establishing the appropriate localisation of structural proteins (e.g F-actin, ZO1) as well as measuring trans-epithelial electrical resistance (TEER).
Schematic diagram and photo of Transwell® insert setup
Following optimisation of the models, differentiated cells are studied by altering their environment, such as exposure to different forms and combinations of inorganic and organic minerals, generating a knowledge-base on the effect of micronutrients on small intestine-like tissue. The tools employed to complete these analyses include microarray analysis for gene expression, mass spectrometry for global proteomic expression analysis, confocal microscopy to study protein localisation and ICP-MS for micronutrient content analysis. Complex bioinformatics tools are used to interpret large scale data sets. The combination of these techniques helps to dissect the intricate effects micronutrients have on the cells and the pathways involved in micronutrient exposure and how best to optimise these interactions.
Capturing images of cell cultures using microscope with Olympus DP70 camera
In order to identify the key issues facing the agricultural industry the Alltech Global Alliance Conference took place on 23rd and 24th March 2015, in Beijing, China. Dr. O’Sullivan and Prof. Clynes presented research for the NICB-Alltech team at the conference.
Group photo of the attendees at the Alltech Global Alliance in 2015
The event saw international academic and industry research groups come together to discuss the latest advancements and issues concerning the agricultural industry. One of the key pending developments highlighted during this conference was “gut health management tools and disease models for defining immunity and productivity”. Following this meeting collaborations were organised between research teams to strategically tackle these issues.
The original proposal between the NICB and Alltech signified an important opportunity to engage a growing multinational with Irish academia. Dr Richard Murphy acknowledged that the level of expertise and research facilities at Dublin City University (DCU) were the primary factor in developing the collaboration, following the original partnership. To recognize the group’s efforts, DCU's President Professor Brian MacCraith presented our team with an award for the partnership with Alltech Ireland at the Invent Commercialisation Awards ceremony on 21st April 2016.
The author with Dr Joanne Keenan receiving the Invent Commercialisation award from DCU President Professor Brian MacCraith at the Invent Commercialisation Awards ceremony on 21st April 2016
The agricultural industry will need to overcome great difficulties in the coming years, as constraints on resources increase alongside population growth. To reach the aim of sustainable food supply within these limitations, scientific advancements surrounding nutrient delivery to both animals and humans is essential.
The Alltech-team at the NICB is comprised of post-graduate and post-doctoral researchers led by Professor Martin Clynes and through engagement with a leading industry partner we are using a range of cell manipulation techniques to decipher and optimise micronutrient supply to animals and humans.
PhD student at the NICB, DCU
NICB-Alltech Alliance group
This industry-academic collaboration is supported by both Alltech LTD. and Enterprise Ireland’s Innovation Partnership Scheme, as part of the National strategy for Science, Technology and Innovation. This research is co-funded by the European Regional Development Fund (ERDF) under Ireland’s European Structural and Investment Funds Programmes 2014-2020.
The NICB team investigate human and animal cells and tissues at the molecular level in order to uncover biological mechanisms and develop new treatments and diagnostics for a variety of human diseases with particular emphasis on cancer, diabetes, infectious diseases, ocular diseases and nutrient uptake.
Alltech is a global leader in the animal health and nutrition industry and one of the top animal health companies in the world. As part of Alltech’s research program a collaborative research initiative was formed with NICB to investigate the role of micronutrient products in cellular health. ONE 17: Alltech Ideas Conference was completed recently and the highlights can be seen in this video.