DCU PhD researcher Charles O’Doherty explains how the NICB is working with industry partner Alltech to promote 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 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 (NICB) and Alltech Ireland have formed a partnership to develop models that allow us to examine how intestinal cells process trace minerals.
The NICB team investigates 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. Meanwhile, Alltech is a global leader in the animal health and nutrition industry, and one of the top animal health companies in the world.
This industry-academic collaboration is supported by both Alltech and Enterprise Ireland’s Innovations Partnership Scheme as part of the national strategy for science, technology and innovation.
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 that 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.
Meet the team
The Alltech team at the NICB comprises postgraduate and postdoctoral researchers led by Prof Martin Clynes, head of the Dublin City University (DCU) research team. Other key members of the project are Dr Richard Murphy, director of research at Alltech and associate research director, and Dr Karina Horgan.
In his role as research director, Murphy is currently involved in multiple areas, including peptide biomarker detection, nutrigenomics, antimicrobial resistance and regulation of protein production. 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.
The DCU team includes Dr Finbarr O’Sullivan (associate director of the NICB), research fellow Dr Joanne Keenan and two PhD students: Ali Coyle and myself, Charles O’Doherty. Other members of the NICB-Alltech team include Dr Niall Barron, Dr Paula Meleady, Dr Padraig Doolan and Michael Henry.
My research background is in cell biology. I completed a four-year biotechnology degree in DCU in 2011 and worked 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. My PhD under the mentorship of Keenan and O’Sullivan is supported by Alltech and Enterprise Ireland.
A multitargeted approach
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 haemochromatosis (for iron). Our team uses a multitargeted 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 (eg sucrase isomaltase) and confocal microscopy establishing the appropriate localisation of structural proteins (eg F-actin, ZO-1) as well as measuring transepithelial electrical resistance (TEER).
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 datasets.
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.
Reaping the rewards
In order to identify the key issues facing the agricultural industry, the Alltech Global Alliance Conference took place on 23 and 24 March 2015 in Beijing, China. O’Sullivan and Clynes presented research for the NICB-Alltech team at the conference.
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. Murphy acknowledged that the level of expertise and research facilities at DCU were the primary factor in developing the collaboration, following the original partnership. To recognise the group’s efforts, DCU’s president, Prof Brian MacCraith, presented our team with an award for the partnership with Alltech Ireland at the Invent Commercialisation Awards ceremony on 21 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.
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.
Charles O’Doherty is a PhD student at the National Institute for Cellular Biotechnology, DCU, and a member of the NICB-Alltech Alliance group.
A version of this article originally appeared on the NICB blog