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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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.

Brainiology Event

Brainiology Event

Guest Post : Tom Butts, University of Liverpool

The School of Life Sciences held a ‘making the brain’ workshop in the Liverpool World Museum on Saturday 21st January as part of the ‘Meet the Scientists: Brainiacs’ day. Members of the public (and more to the point, their kids) came along and had a go at a number of activities all designed to get people thinking about the brain, how it works, and how it has evolved.

The first activity was to ‘build a brain’, where people had to assemble a 3D life-size anatomical model of the human brain. The second was ‘evolving the brain’ and involved arranging a number of animal photographs on a large phylogeny (of vertebrates). The final part was to try and match up the pictures of the animals’ brains to the correct animal on the phylogeny as a way to think about how brains have evolved. I had some cracking volunteers, including postdocs, PhD students, Masters’ students, and undergrad students from across the biological diaspora in Liverpool, and it was a cracking day had by all. Though knackering. I now have even vaster levels of respect for primary school teachers.

Providing new hope to patients with difficult-to-treat Rheumatoid Arthritis

Our hands do a lot of work for us on a daily basis, from tying our shoe laces to typing emails. We may take the work done by our hands for granted, but imagine if moving your hands and fingers was so painful that even the simplest task, such as getting dressed or making a cup of tea, felt impossible. This is what every day feels like for people living with rheumatoid arthritis. While there are medications available to treat some forms of the disease, occasionally patients won’t respond well to these treatments and find themselves unable to do even the easiest tasks. Dr. Helen Wright, a research fellow here at IIB as part of our Molecular Basis of Therapeutic Targeting research theme, is focused on learning more about this disease and developing new ways to screen patients. This research will better enable doctors to work with individual patients in order to find their best treatment options available.mbtt_group-photo-2

Helen has been here at the University of Liverpool since earning her PhD in 2009. Her research focuses on the role of neutrophils in autoimmune diseases, including rheumatoid arthritis. Neutrophils are the most abundant type of white blood cells, with billions of these cells circulating in our blood stream. They are the blood cells that provide us with fast, ‘first-line’ protection against infection. When these cells are working normally, neutrophils patrol the blood stream and when they come across any bacteria, fungus, or other ‘foreign’ invader, they secrete toxic chemicals that can break down and kill the infecting agent. This attack causes the inflammation and red colouring that you’ll see on your own skin when you get a small cut or scrape.

But neutrophils sometimes don’t attack just foreign invaders: in autoimmune diseases, there is a widespread activation of neutrophils, and they’ll attack your own cells with these toxic chemicals in the same way that they attack an infection. Rheumatoid arthritis happens when these hyper-active neutrophils get into joints and cause inflammation and a break-down of cartilage. “Patients with arthritis have many joints – including hands, feet and knees – that are in a lot of pain, and even basic things like brushing their hair become very painful and difficult. Many people with manual jobs, or any sort of work that involves using their hands or having to stand for long periods of time, will have to quit their jobs”, Helen commented. Over 500,000 adults in the UK live with the disease, and in general many people do well with standard drug treatments, with only occasional disease flare-ups. But a small yet significant number of patients have extreme forms of the disease and don’t respond at all to standard treatments. These patients find it difficult to complete simple tasks such as cooking or getting dressed without significant help.

mbtt-wright-figureHelen’s research group is studying how autoimmune diseases manifest and how diseases like arthritis can be better treated for the patients that don’t respond well to a typical drug regimen. One of their approaches is to focus on how arthritis drugs target neutrophils. “We know that these drugs work in reducing inflammation and arthritic symptoms, but we don’t know exactly how a lot of these drugs work, or how these drugs specifically alter neutrophil activation”, Helen said. Having a better understanding of how these drugs work and what properties allow them to target neutrophils can allow for the design of better and more effective drugs in the future.

While Helen’s group is very active and focused on a diverse set of topics, one of her most exciting projects is in finding out ways to tell if a person will respond well to a typical arthritis drug regimen or not. Helen’s approach – an example of personalised medicine – is to use gene expression differences between patients who responded well to drugs and those who didn’t. This data is then used to see what biomarkers could be developed as a way to screen patients before therapeutic treatments begin.

By looking at differences in gene expression, Helen has been able to find out what genes are more prevalent in patients that respond well to drugs and those that don’t. Using a method called RNA-seq, Helen’s group has taken RNA (the form that expressed genes take after they are copied from the genomic DNA) from patients who respond well to treatment and those who don’t. Her group has identified which genes are expressed at higher or lower levels in patients who do or don’t respond to therapy. This allowed Helen’s group to identify two separate groups of genes that are only expressed in responders (10 genes) or non-responders (13 genes) to treatment and these genes are able to distinguish the two groups of patients.

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The next step of Helen’s work is to develop these biomarkers as a tool that can be used by clinicians to predict if a patient will or won’t respond to a drug therapy. “By doing these predictive screens, you can save time and money by not giving a standard drug to someone it won’t work for, and you can focus that time and energy on getting them on a treatment that will work better for them.” says Helen about the importance of being able to use these screening tools in the clinic.

The next step is also one that will require a new set of collaborations and experiences: setting up a full clinical trial. Helen is currently working on grant proposals to get the trial off the ground, one that will involve over 200 patients, at least six collaborating research centres and medical clinics, and patient follow-throughs of up to 12 months after the trial. The clinical study in its entirety will take almost 3 years from start to finish.

“This is my first time being involved with a project as big as this, and I’ve realised that scaling up this project into a national study will take a lot of time and energy. In this field, you go from the science to the clinical aspects and then into the legal and business side of things, and I’m completely new to the legal and business aspects of this work.” said Helen.

When Helen isn’t busy analysing data or writing grants for the clinical trial, she can be found either in the lab or in the hospital working with patients, doctors, and researchers. She and her group members are all trained to take blood on healthy individuals and can be found regularly recruiting fellow staff at IIB for blood donations. “We need to have fresh neutrophils for our experiments in the lab,” Helen said, and admitted that she and other members of the group have had their fair share of blood drawn from themselves to get enough samples to work with.

In the hospital, Helen and her team visit arthritis clinics to collect blood from patients, with all collections done on a volunteer basis. They work with clinical specialists to identify patients with rheumatoid arthritis who have varying responses to drugs and then Helen and her research team will talk with each patient about the work they are doing and what its impact will be. Since blood is already taken as part of a normal screen, it usually takes very little additional time to provide a research sample by filling an extra couple of collection tubes with blood.

Helen has found that most patients are generally interested in what her group is doing and are happy to help. “You have to say that the work you’re doing won’t directly impact the patient themselves but could instead help a future patient. So when you talk to patients, you have to have an altruistic angle in how you talk about the work.” Helen said. “The only reason we have so many drugs to treat rheumatoid arthritis now is because some patients in the past donated their blood for research, to benefit the patients of today”, she added. “Someone diagnosed with rheumatoid arthritis today has a much better chance of being treated in a way that prevents serious damage to their joints than someone diagnosed, say, 30 years ago. But we still have a lot of work to do, particularly for those patients with very severe, hard-to-treat, rheumatoid arthritis.” commented Helen.

While Helen’s career is driven by her degree and background in molecular biology and biochemistry, her passion comes from having a connection to people and patients in her work. “I spent a lot of time studying signalling pathways in university but I was always more of a people-person, and I wanted my work to focus on treating human diseases. I like my job because it feels satisfying to have this balance between science and connecting with people,” Helen said. Helen received her undergraduate degree from the University of Central Lancashire as a mature student and was 35 years old when she completed her PhD at the University of Liverpool. She transitioned into research with more direct clinical applications by collaborating with doctors in the rheumatology clinics at the Royal Liverpool and Broadgreen Hospital and University Hospital Aintree. She is very passionate about her research and at the end of her PhD was awarded an Arthritis Research UK Foundation Fellowship to support her work.

Helen enjoys that each day is very different, with time spent analysing data, working with students and postdocs, and visiting hospitals and clinics to talk to patients. “By far the best part of my job is talking to patients, explaining the science of what we do, and convincing patients and clinicians to help us out. I’m really driven by the human side of research. There are so many patients with rheumatoid arthritis that are so hard to treat, but if we can find a better way to find out who these patients are, it can help doctors find better treatments for them so they can get back to living their lives freed from the pain of arthritis.” said Helen.

If you want to see Helen’s group in action, check out their video:

From Genomes to Biological Systems: Understanding molecular machinery

Our lives are surrounded by man-made structures, from the simple self-assembled furniture in our homes to the massive bridges and motorways that connect cities and countries. Regardless of how complex a piece of furniture or a bridge may be, there needs to be a blueprint in order to make the pieces fit together and function as a whole.

But what about the structures that aren’t man-made, like the proteins and cells in our body? How are these complex biological structures put together, and can we learluning-liu-1-2n how to use these biological blueprints to build cells of our own? Dr. Luning Liu, a research fellow and tenured lecturer at IIB, is working with his interdisciplinary group to better understand the blueprints that describe how living organisms are put together.

Luning came to the University of Liverpool in December 2012 and has been a tenured lecturer since July 2015. The Liu lab is focused on learning how nano-scaled biological machinery are assembled, and one of their interests is in how the parts of algae cells that control photosynthesis are put together. “During photosynthesis, the specialised cell membrane converts solar light into the chemical energy that supports the life on Earth, and we’re using cyanobacteria to understand how these cells build devices that can capture and convert light energy. We can then use that information to learn how we can build our own devices that we can use to enhance the movement of energy within a cell” said Luning.

Cyanobacteria are known as ‘blue-green algae’ and are a type of bacteria that get their energy from the sun. During photosynthesis, the energy from light hits the external membranes of the cell, which break down water into oxygen molecules and generate protons (in the form of hydrogen atoms) and free electrons. The protons are then used to produce energy molecules that the cell can use to generate sugars, amino acids, and starches through the Calvin-Benson cycle. These bacteria have also developed specialised carbon fixation mechanisms, using biological structures known as carboxysomes. Carboxysomes are used to help bacteria get enough carbon so they can complete photosynthesis. g2s-ll-figure

Luning and his group are working on how the photosynthetic machinery in cyanobacteria is organised and how the cells optimise these biochemical reactions to efficiently harvest solar energy and accumulate carbon. In a recent publication from the Liu lab, his group were able to add fluorescent tags to the carboxysomes. These tagged proteins allowed them to track the location and amount of the carbon-trapping carboxysomes while the bacteria were growing. The Liu lab were able to see first-hand how carboxysome movement could be linked to the energy state of the bacterial cell and how they allow the cyanobacteria to optimise how carbon is uptaken depending on the amount of light present.

One of the big picture goals of Luning’s research isn’t just to better understand photosynthesis and carbon fixation, but to work towards design systems that are more efficient, especially in terms of food and biofuel security. “Our goal is to improve the process of photosynthesis so we can improve yields of a wide range of food crops” Luning said.

One challenge faced by the Liu lab is the role of their work in the realm of genetically modified organisms. While his group works primarily on fundamental research, he has encouraged members of his group to be ready for questions on the topic when doing public engagement work and when applying for grants about their research.“Our research has potentially a lot of promise to make a difference but we have to be solid on understanding technology and the mechanism before we can apply them in the real world” added Luning.

Luning and his group work with plant scientists, biophysicists, chemists, synthetic biologists, and microbiologists: a truly interdisciplinary approach towards a better understanding of these complex biological structures. Luning commented: “Nowadays all work in science is multidisciplinary, and you can’t use one technique to solve everything.  The advantage in our group is that there are advanced technologies that we can use to bring our ideas to life. We can ask questions about how natural structures are built in the cells and then work with plant scientists who are looking for a fundamental understanding of the system to see what approaches and techniques they use.”

Luning regularly sends students to technical workshops so they can gain more knowledge and training in the latest technologies and techniques. However he also makes sure that he and his group stick to the basic principles of the scientific method. “I focus on the question more than just the technique by itself. You can use lots of different techniques and technologies to do science, but having a clear question is the most important starting point. The biggest challenge is that there is no one who can tell you what will work, so you really have to explore lots of ideas and try a lot of things before you get something that works” said Luning.

Luning received his undergraduate degree in Biochemistry before earning a joint PhD in microbiology from Shandong University (China) and Leiden University (Netherlands). After spending 2 years carrying out research on biological membranes at the Institute Curie in Paris, he started working on cyanobacteria as a researcher at Queen Mary University of London before joining IIB in 2012. Luning describes himself as driven by curiosity: “Every day is exciting; there are new technologies and papers to keep up with, working with my students on their projects, and reaching out to new collaborators. I enjoy discussing and exploring new ideas by working with colleagues in such an open-minded work environment at IIB.” g2s-group-photo

The Liu lab currently consists of seven PhD students, one post-doc and one technician. Luning works to recruit a multidisciplinary team in his lab, including researchers specialising in molecular biology, biochemistry, biophysics, and plant science. This diverse approach allows group members to learn from one another and enables them to approach problems with different types of perspectives. “Sometimes the biology students have a hard time with the physics, so having a diverse team with diverse sets of skills and knowledge is crucial to making these complex experiments work.” Luning commented.

Luning can regularly be found working in the lab alongside his students and post-doc while encouraging his students to enjoy this time in their research careers as much as possible. Luning replied when asked what his students thought about having their boss pipetting alongside them: “Being a PhD student is the most exciting time in a scientist’s career, because it’s a time when you get to focus on the research and not have to deal with the stressors of applying for grants and funding. I try to help them enjoy this time as much as possible and to help them out.”

Luning is also focused on achieving his own life-work balance, spending the hours from 9am to 5pm in the lab and office before heading home to spend time with his two young children. He then finishes off the evening hours with grant applications, papers, and emails. “The job can be very stressful, especially since this is a very new area, and I try to work hard to stay on top of things. It’s also tough since my kids need my time too, so I don’t go to as many big conferences now so I can spend more time with my family. It’s important to make time for family and do things apart from work”.