IIB visit from Alzheimer’s Society research grant monitors

IIB received a visit on Thursday 15th June from a group of public volunteers who act as lay reviewers of research grant applications and also monitor ongoing research funded by the Alzheimer’s Society. They were hosted by Prof Jerry Turnbull who is currently undertaking preclinical research funded by Alzheimer’s Society on candidate heparin-based drugs aimed at lowering amyloid levels. It is hoped that these might provide a safe early treatment to tackle an underlying cause of the disease, since current treatments only tackle disease symptoms. The research monitors were taken on a tour of the lab and updated on progress with the ongoing project. This was followed by lunch and lively discussions with Jerry Turnbull, Ed Yates and Jill Madine and their lab members.

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Dementia Awareness Week Public Engagement Event

Dementia awareness week (15th – 20th May) has all been wrapped up, and in light of the event Dr Jill Madine and her amyloid group (Kieran Hand, Dr Hannah Davies and James Torpey), Prof Jerry Turnbull and Dr Scott Guimond (Institute of Integrative Biology), and Prof Alan Morgan (Institute of Translational Medicine) participated in the Alzheimer’s Research UK North West public engagement event hosted by the University of Salford on Wednesday 17th May 2017. To celebrate the grand opening of the Universities new Dementia hub, scientific researchers from the University of Manchester, MMU, University of Liverpool, University of Salford and Liverpool John Moore’s engaged in an academic event in the morning showcasing what dementia research is taking place at each institution, followed by an afternoon demonstrating their on going efforts to tackle this life changing disease… to the public!  A breadth of “hands on” activities were available for all ages, and we also invited Liverpool Life Sciences UTC to get stuck in and showcase their ongoing collaborative projects! Activities ranged from how worms are really changing the way in which we can study dementia (with some brilliant videos) (Morgan group), how a ‘spoonful of sugar’ could help treat dementia (Turnbull group) and all the way to what dementia means to you (Madine group). In this activity, the Madine amyloid group asked individuals or groups if they could write or draw their feelings on dementia, have their photo taken with their work, where the public were delighted with the idea that it’s going to be made into a collage for others that were unable to attend the event to see. There were some truly incredible thoughts on the subject from individuals who had been directly impacted by dementia, and as a group we were incredibly humbled by the positive responses to our ongoing efforts in Alzheimer’s, Parkinson’s and associated disorders. See you next year!

“Microbes around us” outreach event with Northwood Primary School, 15.03.17

Written by Jo Moran

Last week Mal Horsburgh and I welcomed Northwood Primary School to the IIB, where they undertook activities to teach them about the microbes that surround us all every day.

In the morning, the students used light microscopes to identify different bacteria that they would come across in their everyday lives. In the afternoon session, the students were taught about viruses, and made their own bacteriophage 3D paper model. The students were extremely enthusiastic, and really enjoyed the chance to use scientific equipment. Over lunch, we encouraged the students to ask questions to the scientists who were demonstrating to them. My favourite questions included “how long does it take to become a scientist?”, “how do you know when you’ve really proved something scientifically?” and “what’s the most embarrassing thing that’s ever happened to you in the lab?”

Although the event was run by Jo Moran, Renze Gao, a Biological sciences honours student, designed and developed all of the activities and resources for the day for his honours project. Renze hugely enjoyed working out how to make what he knew about microbes accessible to 10 year olds, and is considering doing something similar in his future career.

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Meet the Scientists – ‘Build-A-Body’

Guest post by Chris Clarke

On Saturday 1st October Dr Chris Clarke and Dr Dada Pisconti from the Institute of Integrative Biology took part in Meet the Scientists at the World Museum Liverpool. The aim of their stand was to convey to the visitors how muscle is made and repaired. There were two activities set up:
1.      Two microscopes displaying samples (from their lab) of muscle progenitor cells fixed at the start (day 0) and end (day 3) of a differentiation experiment where individual cells at the start of the experiment fuse into multinucleated muscle fibers, replicating in vivo muscle formation and regeneration. A laptop was also set up showing a time lapse video of the same process.
2.      The Muscle Regeneration game. To show guests the process of muscle regeneration in a more hands-on way, a game was set up here children were asked to repair broken Play-doh ‘muscle fibers’ using Play-doh ‘stem cells’. The aim of the game was to split the stem cell in half, turn one half into a new part of a muscle fiber (ie. A sausage) and fix the broken fiber by ‘fusing’ this new fiber with the broken one. 2-3 sets of broken fibers had to be repaired in this way, with children facing off against siblings/friends/parents to finish in the fastest time possible.

They were also assisted on the day by undergraduate students from the University of Liverpool.

Find out more about future events here.

Marvellous Medicine at Meet the Scientists

Guest post by Rorie Hather

Meet the Scientists” is a regular programme of events that takes place at the World Museum Liverpool and organised by the University of Liverpool’s Faculty of Health and Life Science with the support of the Wellcome Trust.  On Saturday 26th November the event drew again a large turnout of visitors. The overall theme was “Marvellous Medicines”. It focused on where our medicines come from, the different methods we use to treat diseases as well as the future of modern medicine. The day involved research teams from across the University of Liverpool lending their time and resources to run eight interactive stalls aimed at ensuring a fun and informative day for the whole family, regardless of age.

Two stalls out of the eight stemmed from different research teams within the Institute of Integrative Biology.  Dr. Raphaël Lévy’s team together with colleagues from the Institute of Translational Medicine (Toni Plagge and his student Joe Robertson) had a stall on “stem cells and nanoparticles”. Dr. Madine’s amyloid group utilised Lego pieces to show how proteins interact with one another and how this impacts their research into neurodegenerative and cardiovascular amyloid diseases.

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Golden? The beautiful colours of gold nanospheres and nanorods in water. The infrared absorption of some of these nanomaterials can be used to image cells in tissues.

The stem cells and nanoparticles stall attempted to translate the ongoing UK Regenerative Medicine Platform work into interactive games to help understand just how small nanoparticles are, as well as showing where stem cells are found within our body and the possible contributions they may be able to have to modern medical science.

A “pin the organ on the human” game was also run, involving visitors placing organ cutouts onto an outline of a human they drew onto a whiteboard, hopefully in the correct place. This game helped to show where exactly our organs are located, and how they each hold stem cells vital to our ongoing health and regeneration. (The freely available resources developed by Eurostemcells are available here if you wish to try this yourself.)  In total, 7 people help run the activity throughout the day: Sumaira Ashraf, Joe Robertson, Elizabeth Grimes, Joan Comenge, Rorie Hather, Angela Midgley and Raphaël Lévy

Dr. Madine’s group used a highly popular tactic among many of the younger visitors. Their game, invented by Kieran Hand and James Torpey, involved using Lego pieces to demonstrate how small molecules can dock to target proteins implicated in the diseases they research. Children were sent on a scavenger hunt around the different stalls to find the hidden complementary shape of Lego that would fit to their existing protein. On their stall, PhD student Kieran Hand said one of their aims was to raise awareness of light chain amyloidosis – a disease that is often left out of the limelight, yet impacts a similar number of people as motor neurone disease. The prizes that had been assembled to give to children who were successful in the drug discovery hunt ran out by 2 pm, showing just how busy the event was. Hammed Badmos also helped on the stall during the day.

The Meet the Scientists series continues into the new year, with the next event, “Brainiacs”, taking place on the 21st January 2017. It will explore the complexities, faults and cures that surround the human brain.

Find out more about future events here.

Building better landscapes for wildlife

Autumn brings shorter days and colder weather here to the UK, with many of us thinking back on the past summer spent hiking, barbequing, and enjoying the elusive British summer sun. Regardless of the outdoor activities you enjoy the most, you’re probably not the only who looks forward to those long summer days. In addition to your neighbours, friends, and fellow hikers, you’ll also find singing birds, pollinating bees, and burrowing rabbits. But as urban areas continue to increase in size while farms continue to use large areas to grow food for growing populations, wildlife are finding it more difficult to have a place to call home. Thanks to conservation biologist Dr. Jenny Hodgson from our Adaptation to Environmental Change theme, IIB is involved with collaborative research with conservation groups for restoring landscapes and building better habitat networks for wildlife populations.

meJenny recently became a lecturer here at IIB and joined the institute as a tenure-track fellow in late 2012. She is currently working on methods to scientifically prioritise where to create new habitats and where to improve degraded ones. But why is this necessary at all, can’t you just restore a habitat anywhere and it will be better than before? “We need to choose carefully because we don’t just want to boost wildlife within the boundaries of our restoration projects. If we choose smartly, we could see benefits cascading away from our projects and long into the future, because we will affect the populations at many sites which are linked together into a network” Jenny commented while describing the key concept at the centre of her research: the theory of metapopulations.

A metapopulation is a group of several wild populations that are linked together by individuals who occasionally disperse between smaller subgroups. Each population inhabits its own ‘island’ of habitat, and separation can be driven between groups by barriers such as roads, buildings, or geographical distance. A well-connected network of habitats can lead to more stable populations than island populations trying to persist in isolation. Conservation groups want to make sure that existing populations are mutually supportive rather than isolated, and they also want to know how to prepare habitat restoration plans for climate change. Increasing temperatures will likely drive animals from their current habitats and into new areas where there may not be adequate habitats for them to move into.

This is where Jenny’s research comes in: her group is using new modelling approaches that can make habitats better connected using the theory of metapopulations. Jenny is currently involved in a research project with conservation groups including the North Pennines Area of Outstanding Natural Beauty and the North York Moors National Park on restoration planning. This project involves developing user-friendly software (www.condatis.org.uk) which conservation groups can use to find the most efficient locations. Efficient locations are where a small amount of habitat increase leads to a large improvement in the conductance, or speed of movement, for the predicted amount of time that a species will spread through the landscape.

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The set-up for the Condatis software is simple: you first input a GIS map of known habitats in your area of interest. From there, you select your source, the habitat that the population will start in, and the target, where you want the population to end up. You also define a typical dispersal distance, or how far a species normally moves around, as well as the reproduction rate of the species you are interested in. No additional scientific knowledge is needed to use the software and the results appear as colour-coded maps and bar charts showing conservationists where the best places for new habitats are.

Within the software, Condatis uses mathematical models which incorporate the principles of metapopulation dynamics to determine how habitat patches connect and how subsequent generations of dispersal and reproduction can lead to the species reaching the target. The software can also identify potential bottlenecks, which are gaps in the habitat network that constrain a population’s ability to reach the target. Focusing restoration efforts on these areas can increase the ability and the speed that wildlife can move around. This also enables wildlife to become better able to respond to environmental or climate changes.

Developing the software was no easy task, and Condatis took a full-time software programmer one year to complete. The project has so far been well-received by conservation groups and people working on habitat restoration efforts. When asked if conservationists are hesitant to use a tool founded completely on mathematical models for restoration decision-making efforts, Jenny replied “The groups we work with do want to know what the limitations of the software are, but in general the conservation groups that come to us think the software is useful. The more the model is demonstrated to work with practical applications, the more people will be convinced it’s worth the time to understand it.”

Jenny is now working to bridge these uncertainties by maintaining regular contact with conservation groups and stakeholders as well as by organizing training events on the use and application of the software. The majority of Jenny’s work keeps her at the office, but she still finds occasional opportunities for getting out into the field. Jenny’s students actively collect environmental data, which allows her group to maintain the connections between the real-world context of conservation planning and to test ecological theories against actual data.

Jenny began her career in conservation biology after earning her undergraduate degree in Natural Sciences from the University of Cambridge. From there she worked at the World Conservation Monitoring Centre in Cambridge, an agency of the UN Environment Programme, as a species program assistant. After working at the Monitoring Centre for 9 months, Jenny found that she craved more of an intellectual challenge and found a PhD on a topic which had inspired her as an undergraduate. Her PhD at the University of York focussed on butterfly metapopulations and involved a combination of field work and population modelling.

Before coming to IIB, Jenny found herself doing a patchwork of jobs, which she used as a time to think about her career and to look for potential long-term leads. “I was lucky I could survive being unemployed for short periods, and I used the time to focus on writing papers. It was a productive but stressful time, and in the end I was able to publish the work from my PhD and a variety of collaborative projects and to show that my ideas were useful for the field.” said Jenny.

Jenny greatly enjoys her time as a researcher here at IIB. “The best part of my job is doing the science, seeing the results first-hand, and connecting with others. The people that I collaborate with in conservation groups are always clever, interesting, and dedicated people with great ideas, and I really enjoy working with people who are involved in both science and policy.” said Jenny. Jenny finds scientific research stimulating, interesting, and challenging, and considers these all to be her motivating factors even amidst the uncertainty and stresses of grant writing and time management in an academic research post. In the next few years, Jenny will be following up with other projects related to the use of the Condatis software, including how to improve movement within marginal habitats, which are areas that can only support a population in the short-term.

While there is still a lot of work to be done in the field of conservation biology and bracing the world for climate change, Jenny is optimistic about the impact of her work. “There is a solution to these problems within wildlife conservation and habitat restoration, and you can see parts of it coming together already. People really do want to see wildlife where they live, but we know that their habitats are eroded and that certain species can’t easily cope with change. While we still don’t know the most effective trade-offs between our needs and the needs of wildlife, we are starting to build smarter ways of better integrating wildlife into landscapes that are full of people.” commented Jenny.

If you want to see the Condatis software first-hand, be sure to check out the tutorial made by Jenny and her PhD student here: https://stream.liv.ac.uk/s/cbufzjp8

A Tale of Two Salmonellas

Thoughts of Salmonella are more likely to get your stomach churning than stimulate your interest. But Salmonella is more than a bacterium that causes a bad stomach ache: certain types of the bacteria can cause serious damage. Professor Jay Hinton, a professor in IIB’s Dynamics and Management of Host Microbe Interactions theme, is finding out how different types of Salmonella cause such a wide range of symptom severity. His group uses gene expression to find out what factors differ between Salmonella subtypes in order to identify new treatments for the nastier types of Salmonella.

Jay has been working on microbial diseases for the past 30 years. In that timehinton, he’s kept a sharp focus on studying Salmonella ever since he finished his PhD. “Salmonella bacteria are great to work with since you can do just about any experiment you want with them. There are also a lot of scientific resources available, including 50 years of research on their genetics and biochemistry. Anytime you work with Salmonella, you’re really standing on the shoulders of giants.” Jay commented.

For over 20 years, Jay has researched the type of Salmonella which is found all over the world, the one you’d likely run into if you happen to eat a bit of undercooked chicken (we’ll refer to it here as ‘Global Salmonella’). He first focused on the role of global gene expression in the ability of Salmonella to make people ill. Jay’s work demonstrates that the more potent types Salmonella express higher levels of certain genes in order to make more of the proteins required to infect their host.

Global Salmonella is a rather innocent subtype. It’s tough enough to survive on dry surfaces and is responsible for severe gastroenteritis in healthy individuals—but there are other far more potent strains. One strain now in focus at Jay’s lab belongs to the ST313 sequence type—the numbering system simply means that it’s the 313th Salmonella type to be discovered. ST313 was first discovered in 2002 in sub-Saharan Africa. Global Salmonella is usually responsible for stomach upsets while ST313 causes a much nastier infection. ST313 kills 20% of the people it infects and the disease is also resistant to 9 antibiotics. ST313 also causes an especially dangerous disease if the patient is immunocompromised by malaria, HIV, or malnutrition. When these patients are infected with ST313, the Salmonella can spread to the liver and spleen and cause severe fever and diarrhoea.hmi-jh-figure“To find ways to cure the disease, we must understand how the infection works. There have been very few new antibiotics made against Salmonella in recent years, so our group is using tools to learn why some Salmonella strains are much more dangerous than others.” said Jay. His group’s approach is to look for differences in virulence factors by comparing Salmonella strains at both the genomic and the gene expression levels. “Looking at the genome alone isn’t enough. The gene content of an organism does suggest potential phenotypes, but if a gene’s not expressed then it can’t cause a change in virulence. The approach we use is to consider both what genes are available and what genes are actually being expressed.” Jay commented.

When looking at the genome itself, researchers focus on natural genetic differences known as single nucleotide polymorphisms (SNPs). A SNP occurs when a single letter in a gene’s code is different between two individuals. Even in organisms of the same species, there are many SNPs that exist between individuals. Because of all this diversity, it’s not always easy to interpret the biological role of particular SNPs. For example, when comparing Global Salmonella and the ST313, there are 1000 different SNPs and over 300 genes which distinguish the two types. “It’s difficult to get information that helps us understand the actual biological differences when just looking at SNPs and genes. So we are using gene expression patterns to map functional information onto these two genomes.” says Jay.

When comparing gene expression between Global Salmonella and the African ST313 types, Jay’s group came across a protein which was much more highly expressed in ST313. Because this protein helps bacteria to survive in human serum, Jay believes that an increase in the amount of this protein allows ST313 to grow and live in the bloodstream. Jay’s group then wanted to understand the mechanism of the increased expression of this key protein, and focused on the nucleotide sequence differences between the two types of Salmonella. They were able to find a key SNP difference in the regulatory region of the gene that actually controls the level of expression.

This work is the culmination of a 4 year project by Jay and his group which was recently been completed, and his group is now getting ready to submit a manuscript for publication. The paper will include experimental work done by several post-docs and PhD students and will include data from infection models that show the role of this protein in causing disease. Jay hopes that the approach of using both genomics and gene expression will be applied by other researchers to identify and validate how other types of bacteria cause disease. “You need to study more strains to gain a broader understanding of how the extremely dangerous Salmonella infections happen.” said Jay.

Jay greatly enjoys sharing his work outside of his scientific community. He finds it easy to connect to others since most people he meets will have some form of a ‘Salmonella’ story. He also thinks that scientists as a whole need to be more proactive at communicating research. “Scientists don’t do enough to talk about the good we are doing. I’m lucky because my field is one that’s easy for people to understand, since everyone agrees that this research on Salmonella is worthwhile. As scientists, it is good to be outward facing with our research. The way we interact with people influences the way they see our work.” said Jay. Jay always strives to be collaborative and open to new ideas, whether it’s working with clinicians in Malawi or sharing techniques with colleagues. “The key for scientists is not to compete with one another but to work together.” Jay emphasized.

Jay started his career by earning his bachelor’s degree in microbiology. “I love microbiology because your experiments will yield results quite quickly—I’m not patient enough for really long experiments!” said Jay. He completed his PhD in plant pathogenesis by identifying virulence genes of Erwinia, the bacterium that causes potato rot. Jay then became more interested in gene regulation and identified Salmonella as the best available model system to study microbe-host interactions. This combination of a great model system and its impact on human health gives Jay his “get out of bed in the morning” factor.

Jay’s day-to-day job involves research, grant writing, and mentoring a group of 6 post-docs, 3 PhD students, and 1 MSc student. He also lectures first-year biology students on topics including “Infections in the 21st century.” When asked about a normal day at work, Jay motioned to his desk piled with papers and books and replied casually “A bit messy!” While Jay did make it a summer goal to clean his desk (which, by the autumn, was halfway finished), he admitted that it was hard to find the time within his endless to-do list. “There’s always more papers to read, another grant to write, or just rushing around from office to office between meetings.” said Jay. Jay also strives to leave time to step back from his to-do list and make time to reflect on ideas, concepts, and to gain new perspectives.

Jay’s group will be kept busy in the coming months with a new research project just funded by the Global Challenges Research Fund. This “10,000 Salmonella Genome Project” involves sequencing Salmonella isolates from thousands of patients in Africa and South America. “By discovering the types of Salmonella that are causing disease across the developing world, we hope our research will lead to new interventions that will improve the lives of people affected by these diseases.” said Jay about the impact of this newly-funded research.hmi_group-photoJay’s group is itself a reflection of the global nature of his work, with researchers from Chile, Spain, Wales, Switzerland, Malawi, Colombia, and the UK. Jay’s research and his group truly embody what it means to be an ‘outward facing’ scientist, including the stuffed microbes that greet you with a friendly smile as you enter his office.

Want to see the Salmonella group in action? Check out their video: