鈥楾ales From The Past鈥�, created in partnership with 91直播鈥檚 leading independent brewery Cloudwater Brew Co, celebrates the University鈥檚 200th anniversary and will be launched at its bicentenary festival, where it will be available to buy from the festival bar.

Supported by a Knowledge Transfer Partnership (KTP) grant, The University of Manchester team crossed Saccharomyces jurei, a new species of yeast discovered by Delneri in 2017, with a common ale yeast, Saccharomyces cerevisae, to produce a new starter hybrid strain that enhances the aroma and flavour of the beer.

This new hybrid has several advantages over similar brewing yeasts; it has the ability to thrive at lower temperatures, adds a different flavour profile, and is able to ferment maltose and maltotriose, two abundant sugars present in the wort. These capabilities provide a range of new opportunities for brewers, with the potential for a multitude of hybrids with different fermentation characteristics.

Paul Jones, CEO of Cloudwater Brew Co, said; 鈥淚t is exciting to be able to brew a beer with a brand new species of yeast and to explore the range of flavours we can create. This beer represents the possibilities of joining academia with industry and we are lucky to have access to this fount of knowledge right on our doorstep.鈥�

The University team has also been developing new hybridisation techniques. Typically, yeast hybrids grow by budding, where a new cell grows from an original 鈥榩arent鈥�, but they are sterile. Now, using a genetic method which doubles the content of the hybrid genome, researchers have overcome infertility allowing the creation of future hybrid generations with diverse traits. These offspring can then be screened for desirable biotechnological characteristics, allowing the team to select and combine beneficial traits from different yeast species using multigenerational breeding.

As yeasts play a major role in many industrial biotechnology applications, different hybrids bred in this way pave the way for creating bespoke microbial factories that can be used to create sustainable products.

As well as their familiar roles in brewing and baking, scientists use yeasts as model organisms to study how cells work. This role has placed them at the forefront of engineering biology, an emerging area of science that seeks to use nature鈥檚 own biological mechanisms to replace current, unsustainable industrial processes. As a result, the team鈥檚 novel yeast could lead to future breakthroughs in new, green pharmaceuticals and more sustainable fuels.

To launch the beer and share more about her pioneering work, Professor Delneri will give a talk at the Universally 91直播 festival on Friday 7 June at 5.45pm. Tickets can be

91直播 is the recipient of five awards, including:

• , Senior Lecturer in Chemical Biology and Biological Chemistry of the , and , Professor of Polymer Science at the Henry Royce Institute, who are a Co-Investigators on a Mission Hub led by the University of Portsmouth. The mission Hub is looking into how engineering biology can tackle plastic waste.
• , Professor of Geomicrobiology, from the Department of Earth and Environmental Sciences, is involved in a Mission Hub led by the University of Kent, and also leads a Mission Award, both of which will be looking at ways to use engineering biology to process metals, including for bioremediation and for metal recovery from industrial waste streams.
• , , and of the 91直播 Institute of Biotechnology, received a Mission Award for a project that will engineer biological systems to enable economical production of functionalised proteins including biopharmaceuticals and industrial biocatalysts.
• , Chair in Evolutionary Biology, from the Division of Evolution, Infection and Genomics, and Professor Patrick Cai of the 91直播 Institute of Biotechnology, are looking into engineering phages with intrinsic biocontainment to develop new treatments against drug-resistant bacterial infections.

The hubs are funded for five years through UKRI and the Biotechnology and Biological Sciences Research Council (BBSRC) and are a collaboration between academic institutions and industrial partners. The Mission Award Projects are funded for two years. These projects will expand upon our current knowledge of engineering biology and capitalise on emerging opportunities.

Announcing the funding the Science, Research and Innovation Minister, Andrew Griffith, said: 鈥淓ngineering biology has the power to transform our health and environment, from developing life-saving medicines to protecting our environment and food supply and beyond.

鈥淥ur latest 拢100m investment through the UKRI Technology Missions Fund will unlock projects as diverse as developing vaccines鈥reventing food waste through disease resistant crops, reducing plastic pollution, and even driving efforts to treat snakebites.

鈥淲ith new Hubs and Mission Awards spread across the country, from Edinburgh to Portsmouth, we are supporting ambitious researchers and innovators around the UK in pioneering groundbreaking new solutions which can transform how we live our lives, while growing our economy.鈥�

Engineering biology has the potential to tackle a diverse range of global challenges, driving economic growth in the UK and around the world, as well as increase national security, resilience and preparedness.  The University of Manchester has a broad range of expertise in engineering biology across its three Faculties and is also home to the international centre of excellence, the 91直播 Institute of Biotechnology.

In Dr Stefan Hoffmann, lead author on the paper, and have found that by adding an estradiol-controlled destabilising domain degron (ERdd) to the genetic makeup of baker's yeast (Saccharomyces cerevisiae), they can control survival of the organism.

Destabilising domain (DD) degrons are an element of a protein that allow for degradation, unless a particular ligand 鈥� a small molecule that binds with the DD degron 鈥� is present to stabilise it. The researchers engineered the yeast to degrade proteins essential for life unless estradiol, a type of oestrogen, was present. Without estradiol, the yeast would die.

This new genetic containment technique differs from previous techniques in that it directly targets essential proteins. It has no detrimental effects on organism function, even when compared with the wild-type organism and it remains an active part of the genome, even after 100 generations.

To achieve this, the researchers tagged 775 essential genes with the ERdd tag and screened the resulting organisms for estradiol-dependent growth. Through this screening, they identified three genes, SPC110, DIS3, and RRP46 as suitable targets. The modified yeast grew well in the presence of estradiol and failed to thrive in its absence.

Professor Patrick Cai, Chair in Synthetic Genomics, said: 鈥�Safety mechanisms are instrumental for the deployment of emerging technologies such as engineering biology. The development of biocontainment systems will effectively minimize the risk associated with the emerging technologies, and to protect both the researchers and the wider community. It also provides a novel solution to combat intellectual espionage to safeguard our ever-growing bio-economy. This work is a great example of the responsible innovation of MIB research.鈥�

Engineering biology is a relatively new, but expanding field of science that allows industry to use microorganisms, such as yeasts and bacteria, to produce value-added chemicals cheaply and efficiently. However, as microorganisms are often genetically engineered to increase efficacy, it becomes a problem if the organisms escape into the natural environment.

To ensure modified organisms do not find their way out of an laboratory setting, the NIH sets strict escape rate thresholds. Currently, most genetic safeguards rely on one of two methodologies to keep within the guidelines: either by engineering in an auxotrophy, whereby the organism relies on a specific metabolite to be present in its environment to survive, or a 鈥渟uicide鈥� gene, where the organism itself produces a toxin that kills it if certain conditions are not met.  

While these methods are generally genetically stable and effective enough to meet the NIH guidelines, they do have caveats to their efficacy. In the case of relying on a metabolite to sustain the organism, this metabolite may also be found in the wild and could not ensure the organism does not survive if it escapes. For 鈥渟uicide鈥� genes, as this is a direct threat to the organism, over generations the gene can selectively mutate and become inactive rendering it an ineffective control.

The new biocontainment method described by Hoffmann and Cai could be used in conjunction with the existing methods to bolster their effectiveness and deliver an even more robust escape frequency. Even if used as the sole biocontainment method, it provides an escape frequency of <2x10^-10 which far exceeds the NIH guideline of an escape rate of less than 10^-8.  

Researchers in the 91直播 Institute of Biotechnology (MIB) at The University of Manchester have created the tRNA Neochromosome 鈥� a chromosome that is new to nature.

It forms part of a wider project (Sc2.0) that has now successfully synthesised all 16 native chromosomes in Saccharomyces cerevisiae, common baker鈥檚 yeast, and aims to combine them to form a fully synthetic cell.

The international team has already combined six and a half synthetic chromosomes in a functional cell. It is the first time scientists have written a eukaryotic genome from scratch.

Yeasts are a common workhorse of industrial biotechnological processes as they allow valuable chemicals to be produced more efficiently, economically, and sustainably. They are often used in the production of biofuels, pharmaceuticals, flavours and fragrances, as well as in the more well-known fermentation processes of bread-making and beer-brewing.

Being able to re-write a yeast genome from scratch could create a strain that is stronger, works faster, is more tolerant to harsh conditions and has a higher yield.

The process also sheds light on the traditionally problematic genome fundamentals, such as how genomes are organised and evolved.

The findings of both projects, published as two research articles of the prestigious journals Cell and Cell Genomics respectively, are a culmination of 10 years of research from an international consortium of scientists led by Professor Patrick Cai and The University of Manchester, and mark a new chapter in engineering biology.

The University of Manchester鈥檚 research also features on the front covers of both journals.

Prof Cai, Chair in Synthetic Genomics at The University of Manchester who is the international coordinator of Sc2.0 project, said: 鈥淭his is an exciting milestone when it comes to engineering biology. While we have been able to edit genes for some time, we have never before been able to write a eukaryote genome from scratch. This work is fundamental to our understanding of the building blocks of life and has the potential to revolutionise synthetic biology which is fitting as 91直播 is the home of the Industrial Revolution. Now, we鈥檙e at the forefront of the biotechnological revolution too.

鈥淲hat鈥檚 remarkable about this project is the sheer scale of collaboration and the interdisciplinarity involved in bringing it to fruition. We鈥檝e brought together not only our experts here in the MIB, but also experts from across the world in fields ranging from biology and genomics to computer science and bioengineering.

Dr Daniel Schindler, one of the two lead authors and group leader at the Max Planck Institute for Terrestrial Microbiology and the Center for Synthetic Microbiology (SYNMIKRO) in Marburg, added: "The international Sc2.0 is a fascinating, highly interdisciplinary project. It combines basic research to expand our understanding of genome fundamentals, but also paves the way for future applications in biotechnology and drives technology developments.

鈥淭he international and inclusive nature of the project has unleashed the science and seeded future collaborations and friendships. The 91直播 Institute of Biotechnology, with its excellent research environment and open space, has always facilitated this."

The tRNA neochromosome is used to house and organise all 275 nuclear tRNA genes from the yeast and will eventually be added to the fully synthetic yeast where the tRNA genes have been removed from the other synthesised chromosomes. 

Unlike the other synthetic chromosomes of the Sc2.0 project, the tRNA neochromosome has no native counterpart in the yeast genome.

It was designed using AI assisted, computer-assisted design (CAD), manufactured with state-of-the-art roboticized foundries, and completed by comprehensive genome-wide metrology to ensure the high fitness of the synthetic cells.

Next, the researchers will work together to bring all the individual synthetic chromosomes together into a fully synthetic genome. The final Sc2.0 strain will not only be the world鈥檚 first synthetic eukaryote, but also the first one to be built by the international community.

鈥淭he potential benefits of this research are universal 鈥� the limiting factor isn鈥檛 the technology, it鈥檚 our imagination鈥�, says Prof Cai.

The research, funded by the Biotechnology and Biological Sciences Research Council鈥檚 (BBSRC) strategic Longer and Larger (sLoLa) grants programme, takes the first major step towards understanding complex microbial communities and will support the move towards a more sustainable and Net Zero future.

The University is one of four institutions to receive a share of 拢18 million from the BBSRC to support adventurous research aimed at tackling fundamental questions in bioscience.

The project, worth 拢5.4 million, builds on the work of the 91直播 Microbiome Network - a network that brings together the leading microbiome science expertise from across the University to deliver a step-change in understanding microbial communities, regardless of habitat.

Lead researcher, Professor Sophie Nixon, BBSRC David Phillips and Dame Kathleen Ollerenshaw Fellow at The University of Manchester, said: 鈥淢icrobial communities, often called microbiomes, are found in almost every habitable environment on the planet. They exert a significant influence on each of these environments, whether that be the soil we grow our food, in the guts of animals, or even in extreme environments like geothermal springs 鈥� our target environment for this project. However, microbiomes are inherently complex and challenging to study, and their 鈥榬ules of life鈥� remain obscure.

鈥淩ecent technological advances have allowed researchers to study the interactions between members of microbiomes for the first time. Yet, we have barely scratched the surface of resolving how these interactions affect the structure, function, and stability of the community as a whole.   

Over five years, the researchers from The University of Manchester and the Earlham Institute will concentrate on low-diversity communities inhabiting geothermal springs, using a powerful combination of biochemical, 鈥榦mics, and synthetic biology approaches to uncover the rules that govern microbial life in communities.

Using a tractable model system, the team aim to engineer the microbial community both as a learning tool to test emerging hypotheses, such as the ways in which microbes depend on or hinder one another, and as a testbed for future biotechnological development.

Ultimately, the findings will facilitate the engineering of bespoke microbial communities to be used for a plethora of important applications, including new ways to bio-convert CO2 emissions into socio-economically beneficial compounds, contributing toward a more sustainable and Net Zero future. 

Professor Guy Poppy, Interim Executive Chair at BBSRC, said: 鈥淭he latest investment by BBSRC鈥檚 sLoLa award programme represents a pivotal step in advancing frontier bioscience research.

鈥淭hese four world-class teams are poised to unravel the fundamental rules of life, employing interdisciplinary approaches to tackle bold challenges at the forefront of bioscience.

鈥淏y fostering collaboration and innovation, we aim to catalyse ground-breaking discoveries with far-reaching implications for agriculture, health, biotechnology, the green economy and beyond.鈥�

The University of Manchester鈥檚 research team includes seven researchers from the Faculty of Science and Engineering (five of which are based in the flagship 91直播 Institute of Biotechnology), two from the Faculty of Biology, Medicine and Health, and one from the Earlham Institute - a life science research institute based in Norwich.