Author: Dr Margaret Rae, post-doctoral research fellow, NUI Galway We are mid-way through the Beaufort Marine Biodiscovery Research Programme, which is aimed at discovery of biologically active compounds (bioactives) and materials for applied applications such as novel drugs and/or materials for use in medical devices. The programme is all about building a national research capacity for the discovery of bioactives and their potential use in the pharma/medical devices area. A sister programme, Nutramara, is looking at the potential use of bioactives as functional or smart foods. Both programmes are funded by the Department of Agriculture, Food and the Marine. The Beaufort Programme brings together researchers from three universities with the support of the Marine Institute: National University of Ireland, Galway (NUI Galway), University College Cork (UCC) and Queen’s University Belfast (QUB). NUI Galway brings biologist, chemist and pharmacist researchers specialised in the identification of marine organisms, the extraction of bioactives from these same organisms, their isolation and purification and finally bioactive identification. UCC brings researchers skilled in the biological arts of identification of the micro-organisms that have the potential to yield bioactives and also compounds that are used by micro-organisms to communicate with each other (quorum-sensing compounds). QUB brings together biologist, engineer and pharmacist researchers targeting bioactives and medical device applications such as bone-tissue formation. [login type="readmore"] MARINE BIODIVERSITY It is now very well recognised that Mother Nature provides us with a natural pharmacy, already packed full of potential drugs and remedies. On land, we have been making very good use of this for as long as mankind has existed. The seas, however, due to their nature are unexplored, yet they are more biodiverse than land. [caption id="attachment_4570" align="alignright" width="1024"] From venous jellyfish to cone snails, all use bioactive compounds for survival and prosperity[/caption] Biological diversity provides us with a molecular biodiversity that has evolved over millennia to interact with biological targets either as chemical defences, offences or as the medium for communication between organisms. From venous jellyfish and cone snails, to territorial sponges and marine bacteria, all use bioactive compounds for survival and prosperity. The seas are a tremendously difficult environment in which to survive; anything that managed to find a foothold can either be quickly covered by other marine creatures, seeking to latch onto something stable, or be eaten. As a result, organisms have developed a sophisticated arsenal of chemicals that prevent or limit this from happening. This arsenal is comprised of many different anti-fouling compounds, anti-feeding compounds, anti-microbial compounds and venous compounds and we hope to find and make use of these compounds in our work. At the Marine Institute in Oranmore, Co Galway, the Marine Biodiscovery Laboratory takes in the marine organisms that other NUI Galway researchers have collected for us. From our coast, Svenja Heesch provides us with the most amazingly coloured sea algae – we see an enormous variety of every hue of red, green, and brown algae, some with wonderful aromas similar to ripening tomatoes and oranges, others very different and all the more memorable for it. Grace McCormack’s group sends us mostly sponges (these are prized producers of bioactives), sea stars and many other invertebrates – again, colour and their alien forms makes these very memorable. We have an abundant coastline, with well over 500 algal species and countless invertebrates – all of which survive and thrive in the wild Atlantic. This coastline provides us specimens practically all year round, come hail, rain or shine. In Ireland, it is mostly the former, so it can be rough getting specimens. There are constraints, of course. One cannot call up the biologists today and ask for a specimen to be delivered tomorrow – it is very much tide and season dependent. Most of the time, we have to wait for low tide, or ask the researchers to dive for it if it is beyond low tide. Of course, it must be the season for it, just as in farming – otherwise, the harvest will be very little and non-sustainable. DEEP-SEA EXPEDITIONS [caption id="attachment_4565" align="alignright" width="1024"] The Celtic Explorer[/caption] From our deep sea, Mark Johnson and Louise Allcock’s expeditions to the our marine Economic Exclusive Zone and the Irish Continental Margin on board the Celtic Explorer research vessel provides us with the opportunity that so many researchers never get – specimens from the deep sea. The deep sea exerts huge pressure on organisms; they are in the dark all the time and at very cold temperatures, so it is not surprising that they have come up with coping mechanisms to survive and thrive under these conditions. Researchers covet the chemical weapons that these creatures have devised – there is a high chance that these have never been discovered before. Louise Allcock is the chief scientist on board the Marine Biodiscovery Expeditions, which we call ‘research cruises’ – cruise is a word that brings to mind luxury, leisure and privilege. Apart from the last, nothing could be further from the truth. It is a working vessel and all on board are there to work, crew and researchers alike. Six-six or eight-eight shifts are set out according to what instrumentation or equipment is going overboard to explore the depths – the CTD (conductivity, temperature and depth instrument capable of taking sea-water samples at different depths), the box core (takes sediments samples at varying depths up to a maximum of 5000m) and finally the remote-operated vessel (an unmanned submersible operated from the desk capable of depth up to 3000m and of taking sediment and plant and animal specimens). It is indeed a privilege. How many of us researchers can say we have been out to sea for three weeks or more at a time and getting such prized specimens for our work? In the Marine Biodiscovery Laboratory, the extracts that we make are run initially against a few in-house bioassays (anti-bacterial, anti-fungal, anti-neurodegenerative and anti-cancer) to verify any initial bioactivity. We send the extracts to our partners in UCC and QUB and to our collaborators for many more and extensive bioassays. What we want to see is some unique and specific activity, that our extract has killed off the bacteria, the fungus, the cancer cells without affecting normal cells. ISOLATION AND PURIFICATION Every time we get a ‘hit’, we get quite excited. This is the catalyst for us to begin the process of trying to figure out which compounds has produced this effect. Now, it is the turn of Deniz Tasdemir’s group in NUI Galway’s Marine Natural Products. Working with Deniz’s team, the bioactive is successively isolated and purified. Deniz was relatively recently recruited and now provides us with the capability of isolating out and identifying the bioactive responsible for some desired activity. At every stage of isolation, we must rerun the bioassays, as it is possible to lose the desired activity. Often, compounds can act in synergy to produce the effect and when we separate these, the activity is greatly diminished or lost. Helka Folch also works in the Marine Institute. She collates all the data being generated at each site and organises it into our Marine Biodiscovery Database. Everyone contributes their piece of the puzzle that’s all brought together in this database. All the specimens, extracts, fractions and bioassays are entered into the database and Helka manages this front and writes the programme for this bespoke database. As more and more is known and as we change direction, Helka is somehow managing to keep track of it all and program in new fields for us to fill in. She also manages the Nutramara database writing the program to keep track of all of this data. Alan Dobson and Feargal O’Gara head up the UCC Marine Biodiscovery activity and Christine Maggs, Brendan Gilmore, Fraser Buchanan head up the QUB effort. For more information, check out the following websites: Beaufort Marine Biodiscovery Project Marine Institute Marine Biodiscovery and Natural Product Research Marine Biotechnology News