Cell division and inflammatory disease link revealed

A ground-breaking study by scientists from the Faculty of Life Sciences and The University of Liverpool scientists has been published in the journal eLife and has identified a new link between inflammation and cell division.

Two of the most important processes in the human body, their accurate control is a holy grail for scientists researching the prevention of infection, inflammatory disease and cancer.

Professor Mike White, who led the BBSRC-funded research and investigates how cells adapt to signals in the body, hit upon the discovery using advanced microscopy and mathematical modelling at the University of Manchester’s world-leading systems microscopy centre and the University of Liverpool’s Centre for Cell Imaging.

“This is an exciting discovery: for the first time we find a link between the system which regulates how cells divide and the basis of some of medicine’s most intractable diseases,” he said.

Inflammatory signals produced by a wound or during an infection can activate a protein called Nuclear Factor-kappaB (NF-κB), which controls the activity of genes that allow cells to adapt to the situation.

Incorrect control of NF-κB is associated with inflammatory diseases, such as Crohn’s disease, psoriasis and rheumatoid arthritis; it has also been linked with ageing and some cancers.

A key way in which human cells adapt to signals in their environment is by dividing to produce new cells through a repeating pattern of events, called the cell cycle. A cell first makes copies of its DNA, in a stage known as the DNA synthesis phase, and then divides into two daughter cells.

The cell cycle is controlled by a family of proteins called E2 factors, which control the start of the new cell’s DNA synthesis phase.

In the eLife study, the team showed that the NF-κB and E2 factors bind to each other in the cell. This controls the level of the NF–κB signal, which is enhanced just before DNA synthesis, but reduced during the DNA synthesis phase.

They also show that signals which activate NF-κB can change the timing of cell division.

The findings suggest that direct interactions between E2 factor proteins and NF-κB enable cells to decide whether to divide and determine how they react in different ways to inflammatory signals.

The work used a set of mathematical equations to make predictions about cell responses, which were then tested by experiments and shown to be correct.

Professor White added:

“We are particularly proud of our combination of maths and experimentation. This is due to the strong support from BBSRC for the area of systems biology and the work of a dedicated team of scientists from different disciplines.”


The paper, Dynamic NF-κB and E2 interactions control the priority and timing of inflammatory signalling and cell proliferation is available. It is available on the eLife website

Tuesday Feature Episode 23: Mike Daniels

This week we feature Mike Daniels, a PhD student who is looking at inflammation! Without further ado, here is his ‘Tuesday Feature’


Please explain your research for the layman in ten sentences or less.

I work on the Immune system and inflammation, which is basically a process where our body releases its troops – the immune cells, in order to fight infection caused by damage of bacterial infection. What I work on specifically is one particular component of this army and that’s called the inflammasome. What’s particularly interesting is that this guy, the inflammasome, actually causes more harm than good. What we’re trying to find out is exactly how this occurs and whether we can produce drugs which will inhibit this inflammasome and hopefully use this to treat inflammatory disease.

mike daniels

How could this benefit the person reading this blog?

The concept of this over active immune system is actually one that I’ve found really interesting. If we’ve got an immune system that is causing us harm, then how has that evolved? This is one of the questions that I would really love to answer. Regardless of that question, this over active immune system process, is involved in a huge number of diseases including Alzheimer’s disease, stroke, malaria, diabetes, cardio vascular disease – all of these disease have a huge involvement with an over active immune system.

If we can understand how this is happening and potentially find ways we can inhibit this response without causing damage to our own immune system, then hopefully we’ll be able to use drugs to treat these diseases.

How did you first get interested in inflammation?

I’ve always been interested in science and one thing that interested me was how drugs were used to treat and cure diseases, so I did pharmacology as an undergraduate. Whilst doing that I got interested in neuroscience and pain. One particular thing about pain is that you think of it as a neural process, but there’s a huge inflammatory component. As I realised this, I discovered that there’s a huge inflammatory component to almost anything you can think of and so on knowing that, I realised what better thing to do than inflammation itself.

Do you have any science heroes? Who inspired you?

I’m not really sure I was inspired by one particular scientist. I always liked the idea of the polymath. So a polymath is someone who is learned in basically everything. I did a school project once on Benjamin Franklin. He was not just a scientist, but he was an inventor, an author, a philosopher and he founded the most powerful country in the world. One really cool thing about Benjamin Franklin that I always liked was that he was one of those really cool types of scientist that just used to test stuff on himself. This is something that I’ve always thought was in days gone by, but in actual fact I had a meeting with someone recently who wanted to know whether or not something was involved in pain. Instead of doing any tests on animals or cells, he just bought it on the internet and injected it in himself to see if it caused any pain. As far as I know, he’s still alive and interestingly it didn’t cause pain. This is something I’ve always inspired to be, a scientist like that – a really cool scientist.

How has working in Manchester helped you?

The Faculty of Life science here at Manchester provided the perfect foundations for me to build a successful PhD. In terms of facilities I have the ability to go to any state of the art facility where I’ll have expert advice on experimental planning, the design and the execution of the experiment and even data analysis. The staff are really supportive and help you build your experiments, but at the same time, they’ll let you go and do your own thing. Also the whole ethos behind the faculty allows a kind of environment where it’s enjoyable to come into work and at the same time we can all still be focused enough to produce successful research. So yeah, thumbs up for FLS.

What do you do outside of work? 

Outside of science, I like to get involved in a lot of sport.  I play football, tennis, badminton, squash – anything I can really get my hands on, although all fairly badly. At the weekends, I like to get myself up a mountain somewhere and do a bit of climbing.

 

Tuesday Feature Episode 12: David Brough

On the back of Gloria’s glowing recommendation, we decided to track down David Brough who is a research fellow within the Faculty. In this episode you’ll get to find out about David’s research into inflammation and how Manchester has helped him as a young researcher.


Could you please explain your research, for the layman, in ten sentences or less?

David Brough holding the Love Life Sciences board.So I work on a process called inflammation which is our body’s response to danger. Unfortunately, sometimes during disease this inflammatory response makes the disease worse. I try to understand these processes to see if we can identify new ways to treat disease.

How does this research benefit the person reading the blog?

So my research is really basic and is at a fundamental level, but hopefully discoveries that I make will, in the future, translate to human benefit. The research I do, for the people reading this blog, will hopefully, in 10, 15, 20 years’ time will have informed some of the treatments or practices to treat inflammatory disease. Inflammatory disease encompasses very common, mainstream disease: Cardiovascular disease, inflammatory skin diseases such as ‎Psoriasis or brain diseases such as stroke or Alzheimer’s disease.

How did you first get interested in inflammation?

I was always very interested in science and biology and I was always interested in basic mechanisms in biology which could contribute to disease. It was during my PhD that I became interested in inflammation. Inflammation is a great area to work in – particularly the processes I work on because there’s so much biology we don’t understand and it is directly relevant to people of all ages because it’s a major contributor to disease processes. It’s easy to understand and justify the reasons for studying these inflammatory processes.

Do you have any science heroes? Who inspired you?

I was always very interested in stories of scientific discovery such as the discovery of DNA and Penicillin. My scientific heroes have always been scientists who have made great breakthroughs. However, there hasn’t really been any one particular person who I inspired to be.

How has working in Manchester helped you?
As a young researcher, Manchester has been a supportive environment and I have great colleagues in my department. They are people who have complimentary research interests and I have been able to work effectively and collaborate well. There have been a lot of opportunities to develop my career.

What do you do outside of work?

When I’m not working here, I have two children who keep me very busy. I do various sports – I’m involved in martial arts and I am a jujitsu instructor, which I do several times a week.


Thank you David for sharing a bit more about your research and your role in the Faculty! Come back next week for another exciting look at some of the people who are involved with the Faculty of Life Sciences.

New discovery provides potential boost for immune disease treatments

Faculty scientists have made a crucial discovery about an immune cell which is used in immunotherapies to treat diseases like type I diabetes.

Dr Mark Travis led a team from the Manchester Collaborative Centre for Inflammation Research who studied regulatory T-cells – important immune cells that prevent harmful immune responses. Their research concentrated on how these T-cells can help cure inflammatory diseases.

Healthy T-CellGenerally, T-cells fight infections and are most useful when acting against foreign invaders in the body like pathogens. However, some T-cells react with our own tissues and cause damage – this is the basis for auto immune diseases like type I diabetes. This is where the regulatory T-cells come in. They help to fight against these rogue T-cells, preventing them causing damage to the body’s own tissue.

Regulatory T-cells are currently being used in clinical trials to help fight auto immune disease. The cells are taken from the patient, multiplied and then given back to them. This helps to suppress their illness.

The team have identified an important pathway by which the regulatory T-cells are activated to suppress the harmful T-cells during inflammation. Dr Travis explains:

“This knowledge is vitally important when trying to make regulatory T-cells for therapy. By knowing the importance of this pathway, we can now work to improve the suppressive nature of regulatory T-cells to make them more effective as treatments for disorders such as type I diabetes and organ transplant rejection.”

He continues:

“It’s fascinating that getting rid of just one molecule can have such an impact on the body’s ability to fight disease. Our research is all about how the molecules interlink and react to each other, and in certain situations targeting just one molecule can boost or inhibit a response.”

The Faculty team demonstrated that the molecules are expressed in both humans and animals. The next step for them is to look at how the mechanism works in practice , using Inflammatory Bowel Disease as a model.

Tuesday Feature episode 3: Dr Jack Rivers-Auty

In week one we caught up with long-standing Faculty professor, Matthew Cobb. Next, we went Stateside to have a chat with alumni Matt Paul. And now, in week three of the Tuesday Feature, it’s time to catch up with a relative newcomer.

Dr Jack Rivers-Auty has been with us for five months, but as you’ll see below he’s already getting into some fascinating research.Dr Jack Rivers-Auty

Jack studies Alzheimer’s Disease, which made him a perfect candidate for this week’s chat, right in the middle of Brain Awareness Week. We hope you enjoy it!

Could you please explain your research, for the layman, in ten sentences or less? 

Alzheimer’s is a disease in which there’s a build-up of an unwanted protein that seems to be toxic to the cells and sets off a chain reaction in the brain that kills neurons. It seems to kill the neurons in the area of the brain associated with memory first and then goes on to kill things in the outer cortex. There seems to be many processes involved and one of the processes is inflammation.

When you roll your ankle it swells up and you tend to put ice on it to mend. This is because you want to reduce the amount of immune cells in there because they produce toxic compounds. We’re investigating whether the diet will affect the inflammatory response in Alzheimer’s disease in a similar way. What we think might happen, and this is just a hypothesis, is that people who are deficient in zinc will be shown to have an exaggerated inflammatory response which causes swelling and tissue damage in the Alzheimer’s brain. So we’re really testing whether having a healthy diet will slow the progression of Alzheimer’s.

How can your research benefit the people reading this blog?

Fingers crossed, and it’s always a long way away because I’m doing pre-clinical research and takes a long time to confirm that the research works in a clinical setting, but it could lead to dietary interventions into Alzheimer’s patients and slow the progression of the disease.

It’s really interesting actually, because older people have worse absorption of micronutrients so having a good diet is even more important as you get older. So the older an Alzheimer’s patient is, the more likely they are to be zinc deficient. The more likely they are to have a hyper-inflammatory response to their condition causing accelerated Alzheimer’s disease.

Can we ask how you first got interested in your area of research?

I guess it goes back to a long time ago. My general area of research is neuroinflammation and I really stumbled into it, which I think most scientists will tell you; they stumble into their research fields.

I did a degree in neuroscience and then I did an honours, which is kind of like a masters, in botany. Then I was looking for a PhD topic and there were several being advertised around the University of Otago, where I’m from in New Zealand. One of them was on the effects of cannabinoids, marijuana like substances, on stroke. This combined my degree and my honours.

Marijuana is anti-inflammatory, so we were seeing if marijuana-like substances could suppress the inflammation following stroke and prevent the swelling, just like the ice when you roll your ankle. What we found was that it did supress the inflammation, but then actually made things slightly worse.

So that was really what it was. I was interested in the combination of botany and neuroscience and that got me into the neuroinflammatory field. But I always want to be a scientist of some kind.

Do you have any science heroes? Who inspired you?Jack at his desk

I have lots of science heroes. This is such a suck-up, but Nancy Rothwell is highly climbing up my science heroes list.

But other than that – oh, there are so many I want to talk about.

Ernest Rutherford – he’s a New Zealand physicist, so that’s why I like him. And he came here to Manchester to do his amazing research. He’s such a hero of mine.

In New Zealand we have this term for doing something on a budget and it’s called ‘number eight wire.’ Fencing wire is number eight wire – you can fix anything with it. It’s the cheap way of doing things. Ernest Rutherford is famous for being the ‘number eight wire scientist’. He was the guy who could just do anything on a budget, and he ended up with Nobel worthy science.

Another guy is Richard Feynman. He’s a physicist as well – damn physicists! But he is fantastic for being incredibly critical of science. He has beautiful commentary on how science shouldn’t get carried away and how there should be proper controls and how we should be really self-critical and self-reflecting. To really produce something meaningful you need to be rigorous and self-controlled, which is what he advocates.

But there’s so many, I could talk for hours.

Can you tell us a little bit about your interests outside of science?

I’d love to say cricket, especially at the moment with the English flying home from the World Cup and New Zealand top of the pool. And I have loads of other interests. I play rugby, I golf, I play cricket, and I surf. I like hiking and I like a lot of activities.

But the other thing, and this is one of the great things about my job, is that I go home and I’ll read a science book. I love science at all times. I’ve got science experiments sitting on top of my fridge right now.

One of my extra-curricular activities is science, which is completely geeky. But that’s one of the great things. I get to do what I love for a job as well as well as going home and doing it. And I write blogs about it. And I read about the latest science and the latest science books that are coming out.

How has working in Manchester helped you?

The first thing I noticed about coming to Manchester is the amount of opportunities that there are. We get emails on a daily basis about millions of things that you can do. You can go see Nobel laureates doing talks, which you could never see where I’m from in New Zealand.

You can do outreach programmes like this through blogs and the Minute Lecture series. I’m also going to schools. So there’s such an amazing encouragement to develop your skills and your outreach here at the University.

The other thing I noticed was that it’s such a team environment. It’s unbelievable. The whole building all gets together and every Friday we talk about the research we’re doing and we get positive feedback. I’ve really just found that amazing – how much of a hive of activity it is and how interested everyone is in other people’s research.

There’s a real team environment. It was an awesome environment to land in when I got here five months ago.

 

And that’s wraps it for this week. Jack has got us feeling extremely positive about the Faculty with that last answer, so we’re off to find our next interviewee!

Our thanks go to Jack – it’s great to see somebody so enthusiastic about what they do. Thanks for reading and please come back next Tuesday!

 

Interview by Fran Slater, Videos by Matthew Spencer, Images courtesy of Nicholas Odgen

Prestigious fellowships for three Faculty scientists

A lab workerOur congratulations go to three Faculty researchers who have recently been awarded important independent fellowships. Gloria Lopez-Castejon and John Grainger received two of the twelve available Henry Dale Fellowships, while Franciska de Vries became the Faculty’s sixth recipient of a BBSRC David Phillips Fellowship.

The Henry Dale Fellowships, which are awarded twice a year, are for outstanding postdoctoral scientists who wish to build their own independent research career in the UK. Gloria and John both work in the area of inflammation. John’s interests focus on the role of lymphoid cells in the regulation of inflammation and immunity, whereas Gloria’s fellowship will focus on how the regulation of certain post-translational modifications of proteins orchestrates an inflammation response.

The BBSRC David Phillips Fellowship, which Franciska has been awarded, is intended for scientists who have demonstrated high potential and hope to establish themselves as independent researchers. There were only five awards available, and the support will last for five years.  Franciska will be researching the role of plant roots in ecosystem responses to climate change. Prof Ian Roberts, Associate Dean for Research in the Faculty, said:

“These fellowships are highly prestigious. To see our promising young researchers recognised in this way demonstrates the calibre of the scientists working in the Faculty.”