Biotechnology and Plastic Reduction

When David Attenborough and the Blue Planet 2 team devoted an entire episode to look at the effect of plastic litter in the marine environment1 they captured the hearts and minds of millions of viewers, but perhaps even more importantly, it seems a tipping point had been reached.
The magnitude of the problem is horrifying. Currently the amount of plastic in the oceans is estimated at 150 million tonnes- about 1/5th of the weight of all the fish in the sea, and by 2050- if things go on unaltered, there will be more plastic than fish in the sea2. Jambeck, J. R. et al. (2015) using 2010 data estimate that 8 million tonnes of plastic get into the ocean every year- the equivalent of 5 grocery bags filled with plastic for every foot of coastline in the world- and the authors warned that this figure could increase 10-fold by 20203. Ocean currents concentrate plastic waste into huge rafts away from the major land masses, and so bizarrely it is often the remotest of islands that are worst littered. One of these rafts has formed a few hundred miles north of Hawaii and is visible from space, being twice the area of Texas, and is said to be dense enough to walk across4. And plastics not just an environmental problem, there is a very strong possibility it threatens human health. The danger posed by plastic increases as it breaks down to tiny pieces in the ocean, increasing the ease with which it can be ingested by marine creatures. As the plastics degrades it more easily releases plasticisers and other chemicals embedded in the plastic, whether in the sea or inside the gut, and also the plastic is able to absorb scents and other natural chemicals in the ocean making the microplastic particles appear more like food to wildlife.
Recent studies have linked found sea bird carcasses stuffed with colourful ocean plastic that led to their starvation and ultimate death, and it’s been estimated that by 2050 all ocean-foraging birds will be eating plastic5. And it’s not just birds that consuming plastic. A 2012 study published by the United Nations Convention on Biological Diversity showed more than 600 species ranging from microorganisms to whales are affected by plastic in some way6. It’s already certain that plastic is in the intestines of the fish we eat, and has been consumed by much of our dietary shell fish7. No-one knows what the health implications for humans might be, so apart from environmental collapse we may also be poisoning ourselves.
But thankfully there is some good news. Recently the media has responded to public interest and is ablaze with images of beaches littered with mountains of plastic refuse, injured marine animals trying their best to pick a living on litter strewn beaches and choked oceans, and perhaps now there is a sufficient momentum to public pressure to bring about change. On this morning’s Today programme a spokesperson for the supermarket chain Iceland promised his company was moving away from plastic packaging and replacing these with modern, effective and sustainable plant based alternatives8 and it seems that this marks the beginning of a more widespread move towards ending the widespread use of plastics for packaging9. Social media campaigns by 38 Degrees, Surfers Against Sewerage, and Greenpeace and others are highly visible, and are playing a vital role in maintaining momentum. All of this must be music to the ears of companies developing non-plastic packaging. For years the economics of replacing plastics with biodegradable alternatives have been stacked against them, and without strong public pressure it is unlikely that any meaningful change away from plastics would happen.
However, going back to having your chops wrapped in grease-proof paper by the butcher is probably not going to happen. The public, whist demanding an end to plastic will also expect functional alternatives that allow them to shop in much the same way as before- and at no greater cost. Happily, there are now many options for sustainable non-plastic packaging10. For instance, why not return to widespread use of glass containers for drinks, bags and nets made from natural fibres for the sale of fruit and vegetables? Most supermarket queues are now comprised of shoppers who carry their own reusable bags, knowing they will be charged otherwise, and there has been an increasing move towards bags made of natural materials. Much of the food we buy however will still need to be shipped and sold in packaging that ticks the same boxes as the awful polystyrene trays and cling wrap we must replace. To this end there is considerable interest in the development of new bioplastics made from for example, keratin from chicken feathers, casein in milk, or polyesters produced by microbial fermentation. These new materials could be either recycled or burnt without the release of toxins, be designed to decompose to carbon dioxide and water rapidly in the environment at ambient temperatures11, have antimicrobial properties for safe food packaging12, and with proper consideration could be produced so as to be greenhouse gas neutral. An important consideration for legislators and policy makers to keep in mind, however, is that these new plastics must not persist in the environment as otherwise we merely substitute the current plastic problem with another.
At IBERs we are doing our bit to help this cause. The BEACON Biorefining Centre of Excellence at Aberystwyth, Bangor and Swansea Universities (beaconwales.org) has a long track-record of working with Welsh companies to develop sustainable technologies. BEACON staff at the BioComposites Centre on Anglesey, have pioneered the development of grass based packaging as part of the Sustainable Ryegrass products (STARS) project that is sustainable, easily composted, and is now used by Waitrose for the sale of fruit and vegetables13. Others research at BEACON is focused on developing novel fermentation processes using non-food plant feedstocks to make sustainable new materials, industrial chemicals and food ingredients, and it tempting to hope that the recent public concern over plastic in the ocean will do much to stimulate renewed interest in sustainable products and bioprocessing.

1. http://www.bbc.co.uk/newsbeat/article/42030979/blue-planet-2-how-plastic-is-slowly-killing-our-sea-creatures-fish-and-birds
2. http://www.telegraph.co.uk/news/earth/environment/12108522/More-plastic-than-fish-in-the-oceans-by-2050-report-warns.html
3. http://science.sciencemag.org/content/347/6223/768
4. https://en.wikipedia.org/wiki/Great_Pacific_garbage_patch
5. http://www.pnas.org/content/112/38/11899
6. https://www.cbd.int/doc/publications/cbd-ts-67-en.pdf
7. http://www.huffingtonpost.co.uk/entry/plastic-pollution-oceans_us_59104e54e4b0d5d9049dc664
8. https://www.theguardian.com/business/2018/jan/15/iceland-vows-to-eliminate-plastic-on-all-own-branded-products
9. https://www.theguardian.com/environment/2017/oct/12/supermarkets-stop-using-plastic-packaging-former-asda-boss-andy-clarke
10. http://www.trendingpackaging.com/the-most-common-eco-friendly-alternatives-for-plastic-packaging/
11. https://lcbioplastics.com/biodegradable/
12. https://www.google.co.uk/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0ahUKEwi_y4zz8tzYAhUO16QKHWwoBq0QFggpMAA&url=https%3A%2F%2Fespace.library.uq.edu.au%2Fview%2FUQ%3A399257%2FPLSE2015_15_CHEVALI_Sustainable.pdf&usg=AOvVaw2vagQDEjS_gc8y4OTqDVNo
13. http://beaconwales.org/en/index.php/blog/view/bangor-university-and-waitrose-branch-out-into-green-packaging

By Dr. Gordon Allison

The wonderland of academic research @Aberystwyth University

There is nothing more exciting in the world of academic research than elucidating the answers for our investigations and further disseminate that particular knowledge. As researchers, we have all been participating to events, symposiums and international conferences and we often been given the opportunity to claim our 15 minutes of fame via the means of a presentation of our projects. There is no need to be shy, we all know that we enjoy it and deep inside feel famous; at the end of the day these events are our Oscars or International Music Awards and if we didn’t end up being nervous and have a panic attack half-way through the talk when realising the audience is bigger than 1000 people we take a step further to establish collaborations and contacts on a global scale.

All that being said, let’s have an imagination exercise and honestly, I hope you will experience the same level of frustration like I do sometimes. Given your results are absolutely breath-taking people will start to approach you to find out more and it usually goes something like that:

“Hi, really interesting work, well done. I am Professor Xavier (fictional) from Harvard School of Sciences.
(automatically you want to re-introduce yourself getting over the raised blood pressure and anxiety levels because you want to represent properly your university and supervisors)
Hello, my name is Adrian (acting surprised even if Prof Xavier has been your supreme idol and you know everything about him). I come from Aberystwyth University.
He will always bluntly reply: Abery….sssst….what?
You imagined he never heard about our lovely coastal rural town in Wales or about the university so you start giving a whole geographical description putting yourself back on his map by which point you notice that he is completely oblivious about the existence of this place as well as confused, thinking this university must be concentrated on agricultural research, etc. and how come you research that topic there?”

As the conversation progresses he is prouder and prouder of your work and you as an individual and the institution itself. Personally, I think the take-away message is to be proud of what you did, where you did it and how you revolutionised that particular field. Indeed, sometimes we might feel that we travelled to the end of the world and Aberystwyth is about 3.5 hours away from everywhere but when we got accepted to study here we definitely been offered the opportunity of a lifetime. Myself, I moved here when I started my degree and I just couldn’t say no to the opportunity of a masters or doctorate. And here we are 7 years later I am still here enjoying my work and stepping further every day towards what I consider my dream career. I met some lovely people here that are genuinely ready to help you, the competition is constructive and the environment is well tailored and facilitated for your research. I have been attending events ranging from non-formal to formal knowledge disseminating activities and I am always pleasantly surprised about the quality of our research in IBERS, thoroughness and approached topics. It is a friendly environment to perform our investigations and Institute wise we are definitely punching above our weight in delivering good quality and innovative research that is recognised world-wide.

Adrian Mironas

Invasive Weed Species as a Source of Antimicrobials – Making the Best of a Bad Situation

Invasive Weed Species as a Source of Antimicrobials – Making the Best of a Bad Situation

Humans have always been dependant on nature to cater for their basic needs such a food and shelter but also for medicines. Initially medicines were in the form of crude treatments such as tinctures, teas, poultices, powders and other herbal formulations. The specific plants and methods of applications were originally passed down through oral history untill the information were recorded in herbals. In more recent history the use of natural products as medicines involves the isolation of active compounds [1]. The first active compound to be isolated in this way was morphine from opium by Friedrich Setürner in 1804 [2]. Drug discovery from plants also led to the isolation of many early drugs such as cocaine, codeine, digitoxin and quinine; some of which are still in use today. Due to the vast diversity of natural products ranging from teraestrial plants to marine organisms also incuding microorganisms and their infinite possible applications the isolation and characterisation for medicinal purposes continues today.
Plants have been the single most productive source of leads for the development of drugs, particularly as anti-cancer agents and anti-infectives [3]. Eventhough natural products have been a plentyful and continuous stream of useful drugs their use has dimished in the past two decade due to the major pharaceutical companies deminishing their interest in natural products. Due to slow nature of natural product discovery and its incompatiblity with high throughput screening (HTS) directed at moleculat targets [4]. Many large screening collections have been dissapointing in practice (these libraries containing a range of compounds from many different sources) natural products are the most diverse class of compounds with a significantly higher hit rate compared to fully synthetic and combinatorial libraries [5]. Furthermore, it has been shown that 83% of core ring scaffolds that are present in natural products are not present in commercially available screening libraries leading to fewer drug leads [6]. It is unsurprisingly that even with the introduction of new methods and technologies natural products have contributed massively to the drugs which have been approved in recent years (see Fig.1).

image1
Figure 1: Contributuion of Natural Products to Approved Drugs between 1981-2010; n=1355. (Adapted from Newman and Cragg 2012 [7])

My PhD funded by the Life Sciences Research Network Wales (http://www.lsrnw.ac.uk/). The project is based on the discovery of antimicrobal compounds form invasive weed species. Invasive non-native weed species are a significant global concern. These are resposible for a loss of biodiversity, altering ecological processes, impacting ecosystem services resulting in a cost of $35 billion annually in the USA [8-10]. If antimicrobial or any bioactive compounds could be sources from these problematic plants then we could at least draw one positive from their unwanted presence within our environment. This project includes the traditional extraction, isolation and characterisation of active compounds form plants followed by biological assays to test a range of biological activites of the compounds extracted. These techinques are also combined with the genomic and bioinformational approaches to aid and improve drug discovery. A wide range of plants were selected for this study and a range of compounds have been extracted from each with a range of interesting biological activites; especially antimicrobial activity. The most active plants tested were Japanese knotweed and Himalayan balsam.

image 2
Resveratrol was found to be the most active antimicrobial compounds present in Japanese Knotweed. This compounds is also found in spermatophytes, such as grapevines and has been linked to a wide variety of biological activites. It has been reported to have antioxidant, anticancer, anti-inflammatory, prevent post-menopausal bone loss, and a range of positive metabolic effects. Resveratrol has also been suggested as the causal link between increased red wine consuption and decreased risk of heart disease [11].
A key compound has been found in Himalayan balsam which is by far the most potant antimicrobial compound in all the plants studied. It has a minimum inhibitor concentration of between 3-15 µg/mL agaisnt a range of Staphylococcal species. This compound has also been found to be non-toxic against mammlian cells. Similar compounds have also been show to have anti-cancer and anti-fungal activity.
The mode of action of these compounds are currently being elucidated using genomic, metabolomic and proteominc approaches combined with novel assays and cytometric techniques. In addition to this I aim to improve the activity of these compounds using computer aided drug design (CADD) through the Life Sciences Reseach Network Wales CADD Platform (http://www.lsrnw.ac.uk/platform-technologies/welsh-computer-aided-drug-design-cadd-platform/).
Natural products have been a source of drugs which have revolutionalised treatment of disease. It is clear that natural sources will contiune to play a significant role in the fight against disease and should be combined with new inovative methods which are currently being developed to form a multidisciplinary approach to treat disease.

References
1. Balunas, M.J. and A.D. Kinghorn, Drug discovery from medicinal plants. Life sciences, 2005. 78(5): p. 431-441.
2. Schmitz, R., Friedrich Wilhelm Sertürner and the discovery of morphine. Pharmacy in history, 1985. 27(2): p. 61-74.
3. Harvey, A.L., Natural products in drug discovery. Drug discovery today, 2008. 13(19): p. 894-901.
4. Harvey, A.L., R. Edrada-Ebel, and R.J. Quinn, The re-emergence of natural products for drug discovery in the genomics era. Nature Reviews Drug Discovery, 2015. 14(2): p. 111-129.
5. Sukuru, S.C.K., et al., Plate-based diversity selection based on empirical HTS data to enhance the number of hits and their chemical diversity. Journal of biomolecular screening, 2009. 14(6): p. 690-699.
6. Hert, J., et al., Quantifying biogenic bias in screening libraries. Nature chemical biology, 2009. 5(7): p. 479-483.
7. Newman, D.J. and G.M. Cragg, Natural products as sources of new drugs over the 30 years from 1981 to 2010. Journal of natural products, 2012. 75(3): p. 311-335.
8. Simberloff, D., et al., Impacts of biological invasions: what’s what and the way forward. Trends in ecology & evolution, 2013. 28(1): p. 58-66.
9. Hulme, P.E., et al., Bias and error in understanding plant invasion impacts. Trends in ecology & evolution, 2013. 28(4): p. 212-218.
10. Pimentel, D., R. Zuniga, and D. Morrison, Update on the environmental and economic costs associated with alien- invasive species in the United States. Ecol. Econ., 2005. 52(3): p. 273-288.
11. King, R.E., J.A. Bomser, and D.B. Min, Bioactivity of resveratrol. Comprehensive Reviews in Food Science and Food Safety, 2006. 5(3): p. 65-70.

Post by Dai Fazakerley.
Dai is a PhD student with Prof. Luis Mur and is one of our Biochemistry BSc graduates.