Science fun at the Gardener’s Question Time Anniversary Garden Party

The Mammalian Behaviour and Evolution Group (MBE) from the Institute of Integrative Biology was represented by four members (Paula Stockley, Holly Coombes, Callum Duffield and Stefan Fischer) at the Gardener’s Question Time Anniversary Garden Party in Ness Botanical Garden. The event saw more than 2000 guests visiting the garden and the live broadcasting of the BBC Radio 4 show. The whole day on Saturday 16th September was reserved for this massive event and the garden staff showed an immense effort to deal with all the visitors and exhibitors.

The MBE group secured a table in one of the huge exhibition marquees next to other exhibitors such as the Wirral Wildlife Trust, RSBP, and the Wirral Barn Owl Trust.

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We showed visitors the diversity of small mammals occurring in the UK with small posters, video clips and, as the highlight, two small rodents to observe. We chose two very different species for visitors to observe: a harvest mouse and a bank vole. Harvest mice are the smallest mouse species and are listed as a Biodiversity Action Plan Species because of their scarcity and the required conservation actions to stop their population decline. Bank voles are a very common rodent species occurring throughout Europe. The harvest mouse was definitely the star of our exhibition and every visitor left with a big smile after finding the little mouse inside the well-structured enclosure. It was particularly nice to see how every person visiting our stand, old or young, woman or man, reacted to the little rodents and how everyone was immediately interested in their behaviour and ecology and asked more facts about rodents in general. We had very nice conversations about topics as diverse as the work of the MBE group, conservation and general behaviour of rodents as well as pest control measurements. I think it was an extremely productive and well received exhibition and visitors of the stand left with a smile because they saw cute rodents and learned more about small mammals in the UK. Moreover visitors will remember that the MBE group of the University of Liverpool is engaged in diverse research areas to better understand and ultimately better conserve mammals in the UK and around the world.

Find out more about the Mammalian Behaviour and Evolution Group.

 

 

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Jerry Turnbull helps raise dementia awareness at charity walk

IIB’s Prof Jerry Turnbull joined 3,000 people this weekend to unite against dementia at a charity walk in the city. He was accompanied by teenager Jay Stout, whose father was diagnosed with dementia just a year ago, at the start line of this year’s Memory Walk in Croxteth Country Park, along with the “Only Men Aloud” singing group (see picture). It is one of two major walks in the city organized by the Alzheimer’s Society to raise funds to fight dementia.

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The Turnbull lab is developing drug candidates based on the blood thinning drug heparin designed to prevent or slow down the development of Alzheimer’s and treat the major underlying cause of the disease for the first time. The work is supported by a £260,000 grant from the Alzheimer’s Society. He said: “This funding was vital for extending our translational studies on safety and efficacy in mouse models, and it was fantastic to see the support by so many people at the Memory Walk.”

 For further information, click here.

Pinfold Junior School day at the Millennium Wood

by Meriel Jones

Getting children out of the classroom to connect with the natural world should be a feature of primary education and is also an excellent way to introduce science.  This is why, towards the end of the summer term on July 5th, children from Pinfold Junior School in Scarisbrick near Southport found themselves in their local Millennium Wood for the day.

Along with building dens, hunting for treasure and making mini scarecrows with their teachers, they went on a bug hunt with Dr James Davies, a postdoctoral associate in the Institute of Integrative Biology.  Extracting creepy crawlies from the undergrowth and then admiring dragonflies and butterflies as they flew past kept the young hunters, and James, very busy.

In addition, Patrick Hamilton, Lois Ellison and Kelly Roper, undergraduate students from the School of Life Sciences Student Outreach Society, were on hand with activities in the local church hall that was the base for lunch. Kelly said ‘We all really enjoyed the day and it has sparked some new ideas for outreach activities we can develop further. Therefore it was a beneficial experience for us as well.’

‘I would say the main thing I took away from the day was how much fun the children had applying what we had told them about adaptations, to the creation of their own creatures which had a whole range of creative/imaginative features.’

This event is the most recent in the Institute of Integrative Biology’s relationship with Pinfold School that began in 2010 and has included a project that won the annual national Rolls-Royce Eden Award for the best implemented environmental project meeting the needs of a school in 2013.

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Meet the Scientists On Tour

Meet the Scientists On Tour

by Rebecca Jones

Meet the Scientists on Tour 

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 Meet the Scientists on Tour is an initiative that aims to bring science to the public in places they don’t expect it. Activities centre around magnetic whiteboards where the public can spot caterpillars or match parasite to their hosts. The founders, Klara Wanelik, Rebecca Jones, Gabriel Pedra and Beth Levick have been visiting a number of locations in Liverpool and a folk music festival in Newcastleton where events ran 11am to 3pm. Here’s what they had to say about the events:

 

St John’s Shopping Centre

The first event was held at St John’s Shopping Centre on the first Bank Holiday Monday (May 1st) and was a success. We engaged with about 40 people although it was so busy we had to work hard to get people to come over to play our activities. It also didn’t help that people thought we were trying to sell them something! We had some great interactions with people though, with comments from participants including: “I really enjoyed the session”, “Caterpillar game – Thank you!” There were also college students asking about studying biology at the University!

 

Central Station

Our second event was run on Saturday 6th May at Liverpool Central Station and was very well received. The public passing through the station got stuck in: spotting caterpillars, spreading infection and matching parasites to their animal hosts!

We engaged more people than our last even at St John’s Shopping Centre (approx. 50) and were pleasantly surprised by how positive people were about engaging with our science in such a busy place! The majority of our visitors were young children aged 2-10 years. However, parents seemed equally as interested and we also had a few questions about studying at the University.   Comments (from some of our younger participants) included: “I really liked the visit. I hope you come again”, “Really fun and interesting,” and “I liked the games because I learnt things”.

 

New Mersey Retail Park

Our final event in Liverpool was at the New Mersey Retail Park in Speke on the 29th May. The weather wasn’t great so we were very grateful for our gazebo! Due to the weather we engaged with slightly fewer people (approx. 25) but we had people actively coming over to the gazebo upon recognizing either the University of Liverpool or Meet the Scientists logo. We even had a small girl run into the gazebo exclaiming that she wanted play games in the science tent!

Overall we had a brilliant time across our three locations in Liverpool and are keen to go back and take along some new activities. However, we found that we were mostly engaging with families or the elderly and missed out on the middle age bracket.

 

Newcastleton Traditional Music Festival

Our most recent location was up in Newcastleton on the Scottish border, close to Kielder Water and Forest Park. We chose this location as Klara is part of a project sampling field voles in Kielder forest and so she was keen to inform the public about what the team was doing. Additionally, we were interested in taking our activities to a music festival as it was a completely new environment for us to do outreach.

We didn’t know what to expect at the festival but it turned out that we were the only stall there and so were able to monopolize the green in the village. On the Saturday (1st July) there were folk music competitions underway but we were able to engage with a large number of local villagers and visitors from further afield. Over both days (4 hours on the Saturday and 1.5 hours on the Sunday) we engaged with a total of 52 members of the public.

We had some great interactions with people, many of whom approached us out of curiosity about why the University of Liverpool was present in Kielder. We were also able to interact with people from a broader age range – particularly with people in their 20’s and 30’s. We had a few local farmers come over who were particularly interested in our ‘Where does the parasite live’ activity. Our competitive game where people spread infections in populations proved very popular again at this event. Furthermore, lots of people were interested in the work with the voles that Klara was describing. Overall, we thoroughly enjoyed carrying out our outreach at the folk music festival which was a very different challenge to the locations in Liverpool. Although, after ceilidh dancing into the morning and being attacked by midges in our tent, we were happy to return to Liverpool for some well-deserved rest!

 

Finally, we would like to say thank you to everyone who helped make ‘Meet the Scientists on Tour’ possible. We’d like to thank the Wellcome Trust for funding us and Laura Winters for her support. We’d also like to thank Vincent Keenan for assisting at the event at Central Station and Steve Paterson for his additional financial (and moral) support. Most importantly, we’d like to thank everyone at the various locations who made it possible (and so enjoyable!) for us to carry out our outreach.

We’re keen to extend our outreach beyond ecology-based activities and so on the 5th July we ran an activity design workshop with attendees from the Victoria Gallery and Museum, Engineering Department and Institute of Translational Medicine. This was a half-day workshop where people had a go at our activities before settling down to design their own. Attendees then had a chance to present their boards, with much discussion in the group. We look forward to welcoming some more activities soon. Watch this space!

 

If you’re interested in designing an activity or want some more information, contact us on twitter at @MTS_OnTour, or by emailing kwanelik@liv.ac.uk.

Quantum dots for Immunofluorescence

Guest post by Dave Mason; reblogged from rapha-z-lab

In modern cell biology and light microscopy, immunofluorescence is a workhorse experiment. The same way antibodies can recognise foreign pathogens in an animal, so the specificity of antibodies can be used to label specific targets within the cell. When antibodies are bound to a fluorophore of your choice, and in combination with light microscopy, this makes for a versatile platform for research and diagnostics.

Most small-dye based fluorophores that are used in combination with antibodies suffer from a limitation; hit them with enough light and you irreversibly damage the fluorochrome, rendering the dye ‘invisible’ or photobleached. This property is the basis of several biophysical techniques such as Fluorescence Recovery After Photobleaching (FRAP) but for routine imaging it is largely an unwanted property.

Over 20 years ago, a new class of fluorescent conjugate was introduced in the form of Quantum Dots (QDots); semiconductor nanocrystals that promised increased brightness, a broad excitation and narrow emission band (good when using multi-channel imaging) and most importantly: no photobleaching. They were hailed as a game changer: “When the methods are worked out, they’ll be used instantly” (ref). With the expectation that they would “…soon be a standard biological tool” (ref).

So what happened? Check the published literature or walk into any imaging lab today and you’ll find antibodies conjugated to all manner of small dyes from FITC and rhodamine to Cyanine and Alexa dyes. Rarely will you find QDot-conjugated antibodies used despite them being commercially available. Why would people shun a technology that seemingly provides so many advantages?

Based on some strange observations, when trying to use QDot-conjugated antibodies, Jen Francis, investigated this phenomenon more closely, systematically labelling different cellular targets with Quantum dots and traditional small molecule dyes.

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Figure 3 from doi:10.3762/bjnano.8.125 shows Tubulin simultaneously labelled with small fluorescent dye (A) and QDots (B). Overlay shows Qdot in green and A488 in Magenta. See paper for more details. 

The work published in the Beilstein Journal of Nanotechnology (doi: 10.3762/bjnano.8.125) demonstrates a surprising finding. Some targets in the cell such as tubulin (the ‘gold standard’ for QDot labelling) label just as well with the QDot as with the dye (see above). Others however, including nuclear and some focal adhesion targets would only label with the organic dye.

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The important question of course is: why the difference in labelling when using Quantum Dots or dyes? This is discussed in more detail in the paper but one explanation the evidence supports is that it is the size of the QDots that hinder their ability to access targets in the nucleus or large protein complexes. This explanation further highlights how little we really know about the 3D structure of protein complexes in the cell and the effect of fixation and permeabilisation upon them. Why for example, can tubulin be labelled with QDots but F-actin cannot, despite them both being abundant filamentous cytosolic structures? At this point we can’t say.

So why is this study important? Publication bias (the preferential publication of ‘positive’ results) has largely hidden the complications of using QDots for immunofluorescence. We and others have spent time and money, trying to optimise and troubleshoot experiments that upon closer study, have no chance of working. We therefore hope that by undertaking and publishing this study, other researchers can be better informed and understand when (or whether) it might be appropriate to use Quantum Dots before embarking on a project.

This paper was published in the Beilstein Journal of Nanotechnology, an Open Access, peer-reviewed journal funded entirely by the Beilstein-Institut.

 

Breaking up is hard to do: New insights into cell signalling revealed

Press release originally issued by the University of Liverpool on June 23, 2017:

A rewrite of biology classroom textbooks could soon be on the cards as scientists at the Universities of Liverpool and Washington reveal important new insights into how cells communicate with each other. The research is published today in the prestigious journal Science.

Cell signalling refers to the mechanisms cells use to communicate with each other. In humans, signalling normally regulates cell growth and repair and therefore contributes to diverse basic processes that control tissue physiology and brain function. However, abnormal cell signalling contributes to many diseases, including diabetes, cancer and neurodegeneration. For this reason, the proteins that control disease signaling are important targets for many types of clinically-approved drugs.

In the new study, the researchers focused on understanding how proteins assemble into higher order signalling complexes, which control aspects of cell communication and cell fate such as the decision to live or die, using the ‘textbook’ cyclic AMP (cAMP) signalling pathway.

In the late 1960s, cAMP was shown to activate an enzyme complex termed Protein Kinase A (PKA), which can exist in both ‘active’ and ‘inactive’ forms depending upon the type of complex assembled.  It had long been thought that cAMP levels were sensed in cells by a release of the active kinase component from the larger PKA complex, rather like ice cubes breaking apart after being added to a drink.

Using contemporary scientific strategies, including electron microscopy, mass spectrometry, chemical genetics and real-time imaging, the researchers found that instead of being broken apart by physiological levels of cAMP, the signalling complexes remain intact, directly delivering the appropriate message into the correct part of the cell interior.

The study was carried out by Dr Dominic Byrne and Dr Matthias Vonderach in the laboratories of Dr Patrick Eyers and Professor Claire Eyers in the Department of Biochemistry at the University’s Institute of Integrative Biology, in collaboration with Dr Donelson Smith and Professor John Scott and colleagues at the University of Washington.

Dr Patrick Eyers explained: “We believe the finding that PKA protein complexes respond to the second messenger cAMP in a different way than we had assumed for nearly half a century, might bring about other changes in how we understand cell communication, especially the type of signaling we study that involves protein modification (phosphorylation) by protein kinases.

“It might also prove important for a better biochemical understanding of how medicines affect PKA signaling complexes, allowing us to develop drugs with fewer side-effects.”

The next challenge for the team will be to try to explain how the larger PKA signalling complex functions in cells, and how it is regulated by various factors.

The research received funding support from the UK Biotechnology and Biological Sciences Research Council, North West Cancer Research and the Howard Hughes Medical Institute.

The paper ‘Local protein kinase A action proceeds through intact holoenzymes’ is published in Science [DOI: 10.1126/science.aaj1669]

The story behind the paper

We recently published a paper on genomic surveillance of a diarrhoeal pathogen Shigella sonnei across Latin America which represented the culmination of over five years of collaboration, as well as training and development in the region

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In collaboration with the Wellcome Trust Sanger Institute, the Pan American Health Organisation and PulseNet Latin America and Caribbean (PNLAC), we whole genome sequenced over 400 Shigella sonnei collected from nine countries over two decades. Shigella are the most important bacterial cause of moderate-to-severe childhood diarrhoeal disease in low to middle income nations, and countries in Latin America still experience endemic disease and explosive outbreaks. By sharing information on common pathogen subtypes through public health networks, like PNLAC, pathogens can be traced epidemiologically to facilitate early identification and intervention in disease outbreaks. Whole genome sequencing is transforming surveillance of bacterial pathogens, as it provides the highest resolution of pathogens subtypes and can also be used to explore other genetic factors of interest, like antimicrobial resistance. However, its cost precludes routine use in some areas, which are unfortunately some of those regions where the most Shigella disease is seen.

In this study, we sequenced approximately 50 isolates from nine countries in Latin America and use whole genome phylogenetics to reveal those sublineages that were responsible for most of the disease in the region. We identified a novel global lineage of Shigella sonnei, and by correlating the geography of where isolates came from to their evolutionary relationships, we could see international transmission of some sublineages and what the distribution of different sublineages was across the continent. Visit the microreact page to play with the data yourself.

We were also able to identify key determinants of antimicrobial resistance in the pathogens and how they were distributed among the different sublineages, providing key information for managing this important disease in the region.

In addition to constructing this invaluable regional framework for ongoing surveillance, this project helped build capacity for whole genome sequencing surveillance in the region. Over the course of the collaboration, the World Health Organisation sponsored the establishment of whole genome sequencing facility at the reference laboratory for PNLAC, ANLIS in Buenos Aires, Argentina (see photo). In the paper, we show how locally-generated sequencing data from this facility can be integrated into the regional surveillance framework to determine whether outbreaks were due to locally-circulating lineages or resulted from the importation of new sublineages.

In addition to laboratory capacity building, the collaboration involved training an ANLIS researcher (Josefina Campos – see photo – who now runs the genomics facility there) in bioinformatics, and conducting training courses (in conjunction with Wellcome Trust Advanced Courses) for medical, veterinary and public health professionals in the region, including courses in Argentina, Uruguay and Costa Rica (see picture).

There are 29 authors on our paper and every one of them worked hard on, and cared deeply about, the outcome of the study as well as the training programs and capacity building surrounding it. Every paper has a story behind it, and this one, like so many others, is so much more than it appears.

Photo: Top ANLIS in Buenos Aires, Argentina. Bottom (from right to left) ANLIS collaborator Josefina Campos and co-corresponding author Nicholas Thomson (WTSI) outside the Malbran (ANLIS) Institute; Genomics for Epidemiology and Surveillance of Bacterial Pathogens course instructors and participants held in February 2015 in San Jose, Costa Rica; co-corresponding author Kate Baker with bust of Carlos Gregorio Malbran, the ANLIS institute’s namesake.

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