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.

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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.

 

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.

Alz Soc visit 15 June no2

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!

More Neuroblastology success!

This year our fruitful collaboration with Liverpool life sciences UTC has continued and we would like to take this opportunity to congratulate Laura Hurst on the success of her Year 13 Project.

Laura has been working on our Neuroblastology programme at UTC and designed and carried out an experiment to investigate the neuroprotective effect of lemongrass on brain cells in Alzheimer’s disease. Laura has cultivated SHSY5Y neuronal cells, exposed them to amyloid beta protein (protein involved in neurodegeneration in Alzheimer’s disease) and explored the protective effect of lemongrass on these affected cells. Laura has now finished the project, written an excellent report and presented her findings to her peers and the teachers at the school.

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This is her abstract from her report.

This project’s main purpose is to explore the potential neuroprotective effects of lemongrass (Cymbopogon Citratus) and how these effects can be utilised in the treatment of Alzheimer’s disease. The rates of this disease have greatly increased over the past few decades and so the development of new pharmaceuticals is increasingly important to society. To test the hypothesis of lemongrass having neuroprotective effects two well plates were set up with neuroblastoma cultures, one of which had beta amyloid protein (one of the key pathological markers of Alzheimer’s disease) added. Three different solutions of lemongrass essential oil were also added (0.1%,0.5%, and 1%) as well as two control groups containing either F-12 Ham’s nutrient media only or 100% ethanol. The results of the experiment suggested that an increase in lemongrass solution reduced the concentration of cells per mm² but increased the viability of the cells in the amyloid beta protein plate. 0.5% lemongrass solution almost doubled the viability of the neuroblastoma from 37.04% in the media only control group to 68.61%. These results support both the Amyloid hypothesis and the hypothesis established for this project, and so it can be concluded that lemongrass has potential as a treatment to Alzheimer’s disease if further research is carried out.

The school are so impressed they are using her work as a model to show students and teachers alike how science project work should be conducted and reported.

We would all like to congratulate Laura on her fantastic success and wish her luck in her dreams to pursue a career in neuroscience!

In more good news, Dr John Dyer at UTC is involved in the process of arranging an exchange programme to enable students from different schools in Europe to work on extended projects at different sites dependant on their interests. UTC (in collaboration with the University of Liverpool) is hoping to make the neuroblastology project their specialty! So hopefully soon we will be welcoming students from across Europe to learn cell culture techniques and do more exciting experiments.

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Postcard from Vienna, Alzheimer’s disease and Parkinson’s disease (ADPD) conference – 2017

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This was a huge display within the conference venue – amazing photography!

Last week three members of IIB, Dr Hannah Davies, James Torpey and Prof. Jerry Turnbull went to Vienna to find out about the latest research and technological advances in the field of neurodegeneration and dementia at ADPD 2017. This five day conference saw over 3000 clinicians, researchers industry specialists from around the globe discuss recent advances in the field, including reports on the latest drug trails, new avenues for treatment and patient perspectives. This busy meeting gave us the opportunity to catch up with colleagues from around the world, and share the exciting research we are doing here at Liverpool with a huge audience.

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The conference venue and an action shot of James presenting his findings at one of the poster sessions

During our stay in Vienna we were treated to welcome reception at Vienna’s beautiful City Hall, we ate traditional Austrian dishes, talked science and enjoyed an impromptu opera performance from one of our colleagues!

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Welcome reception in the impressive Vienna city hall

We came away from the conference, tired but full of new ideas and renewed enthusiasm for our projects.

Science week in Mosspits Lane primary school, 6-7 March 2017

As part of her honours project Mary Roughley visited Mosspits Lane Primary School in Wavertree, Liverpool, during Science week. She has spent an afternoon with each year 6 class and engaged with the pupils on topics such as scales in the universe, the concept and calculation of magnification and the power of using microscopy in biology. As part of her honours project, Mary has planned the session and developed the supporting worksheets and instruction protocols. After a short presentation, the whole class went out onto the playground to collect their own live samples to view under the microscope, the class were then split into three groups to rotate between the three exercises that were organised. The most popular activity was collecting and viewing their samples. The pupils were given magnifying glasses and also had access to the Zeiss stemi labscope to enable them to examine their specimens. They collected insects, worms, leafs, bread crumb, aphids, hairs…They really enjoyed this activity and were fascinated and very excited by what they could see with a microscope: worms digestive tubes, tiny unsuspected hairs on insect legs and “a starry night sky” (salt imaged with transmitted light)!

The pupils also made their own magnifier using water in petri dishes. They learnt how to calculate magnification and used this knowledge to calculate and compare the magnification of a magnifying glass and the magnifier that they made. They realised that their magnifier made with a drop of water was as good as a commercial magnifying glass.

For the third activity, the pupils used the schools computers and an online programme to learn more about scales. The software showed objects of different sizes ranging from galaxies to a proton nucleus. This activity reinforced the idea that microscopes are essentials to biologists, as many things are much too small to be seen with the naked eye. This is what Mary says about her experience: “I received excellent feedback from the pupils. They thoroughly enjoyed the session and some mentioned that they would like to become biologists. They particularly enjoyed using the microscope and collecting their samples and a number of pupils said that the only bad part of the session was packing away! As a proof of the success of the half-day, the teachers had to fight for the children to go out at playtime. They preferred observing their samples under the microscope. I have personally really enjoyed delivering the sessions, I found the experience very rewarding especially when the pupils said they wanted to be biologists! The experience has also made me consider teaching as a career.” This is what the children wrote about the session: “‘I wish the session was longer!!; I liked seeing the intestines in the worm, it was gross but cool!; The bacteria in the pond water was really cool.” It was a very enjoyable experience at all levels: for the children, the teachers, the undergraduate student involved and me, the academic supervisor. Thank you to Mosspits Lane to have worked with us on this project.

Violaine Sée, IIB