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Ticking Body Clocks: Research in Life Sciences

by YPU admin on February 4, 2016, Comments. Tags: biology, Body Clocks, Life Sciences, Neuroscience, Research, and UoM

Introduction

My name is Charlotte Pelekanou and I am a PhD student at the University of Manchester studying Circadian Biology (body clocks). Body clocks are found in all body organs and gives time of day messages to lots of body processes. Altering these clocks can lead to the development of obesity and type 2 diabetes (when your body does not regulate your blood sugar properly). Before starting my PhD, I did my undergraduate degree in Biomedical Sciences and masters in Neuroscience research, both at the University of Manchester.

In Depth

Why am I interested in body clocks?

When I tell people I research body clocks they always think of sleep. However, over the last 50 years circadian biology has expanded massively as more and more is found out about how the clock affects our body functions.

 I became interested in the body clock because a family member had an illness that made them have problems with their sleeping. I then found out in my undergraduate degree that the body clock does more than regulate sleep; it also has effects on most bodily functions including processing the food you eat, how your immune system protects you and how you store memories.

I then chose to do a PhD on the effects of the clock on obesity and diabetes as obesity is a growing issue in current society and it costs the NHS a lot of money to treat patients who have health problems as a result. I am also really interested in circadian biology itself as I like the concept of ‘social jetlag’, where people are living in a different time to their body clock, and how increased use of technology such as mobiles and iPads in the evenings can lead to negative health effects and contribute to this rise in obesity. I am also interested in the concept of chronotherapy which is looking at how taking drugs at different times of day can have an effect on how well the drug works. All of these make circadian biology a really exciting research area.


What do I research specifically?

During my PhD, I am looking at the clocks involved in metabolism (how food is used to get energy) and the immune system and how altering them can lead to negative effects on your body. Particularly, I’m looking at inflammation in fat tissue caused by obesity and how it leads to the development of type 2 diabetes.  It has already been found that people who work shifts, like doctors and nurses, can have an increased risk of becoming obese and getting diabetes. This happens because your internal timing is set to a different time to when you are working, such as being awake and eating meals during the time your body wants to be asleep. As we have already found that the body clock is linked to metabolism and the immune system, we are looking for the specific pathways in metabolism and the immune system that are linked to the body clock and how they are changed with alterations in the body clock. We then want to see if we can modulate the pathway to remove these effects of inflammation in obesity so that fewer people would get diabetes from being obese.

Going Further

·  You can test when is the best times for you to go to sleep and wake up: http://www.bbc.co.uk/science/humanbody/sleep/crt/

·  You can look up when is the best time to sleep, eat and exercise:

http://www.bbc.co.uk/news/health-27161671

·  Some excuses to start school/work later:

https://www.youtube.com/watch?v=4PSZ76rFZS0&index=11&list=PL9uTU-SI30pTlVyigGcnvDgHpDAFo4AEP

http://www.telegraph.co.uk/news/science/science-news/11851311/Staff-should-start-work-at-10am-to-avoid-torture-of-sleep-deprivation.html

·  Here are links to interviews with circadian researchers at The University of Manchester

https://lsmanchesterblog.wordpress.com/2015/06/23/tuesday-feature-episode-17-qing-jun-meng/

https://lsmanchesterblog.wordpress.com/2015/06/16/tuesday-feature-episode-16-andrew-loudon/


 

Using The Force: Cell Signals

by YPU Admin on October 2, 2014, Comments. Tags: biology, cells, and Research

Introduction

My name is Ben Stutchbury and I am a second year cell biology PhD student, looking at how cells sense and respond to the environment around them. I did my undergraduate degree in molecular biology, which I also did at the University of Manchester.

For a long time, the way that cells sense and respond to the environment around them was thought to be only due to chemical signals. Cells produce different chemicals and proteins that attach to other cells, transmitting a message and triggering a response, just like sending and receiving a text message. However, recently it has been seen that cells are also able to sense and respond to mechanical signals, rather than just chemical signals. I am trying to figure out how cells are able to do this, and the important role that these mechanical signals play in the cell.


In depth

The mechanical properties of different tissue types vary all over the body. Brain is extremely soft, muscle a bit stiffer and bone the most rigid. Studies have shown that these different mechanical properties can affect several different aspects of cell behaviour such as how fast they grow, how quickly they move or even affect what type of cell they become.

Now imagine you are a cell, how do you know where you are? Cells don’t have a sense of sight, smell or hearing, but… they do have an extremely sensitive sense of touch.

Hundreds of proteins come together in a defined and intricate order to form streak-like structures known as focal adhesions (shown in green in the picture). These form at the edge of the cell, and reach outside, literally grabbing onto the surrounding environment. Basically acting like a cell’s tiny hands. Using these hands, the cell then blindly pulls and probes on the external environment, feeling its mechanical properties and the forces acting on the cell. Now, as I said before, as well as feeling their environment, cells will also respond it. If the environment around it changes, for example becomes softer or stiffer, then the forces acting on the cell will change. The cell, via its focal adhesion hands, is able to feel and respond to these changes. They are quite literally using the force! This signalling is extremely important for the cell to function correctly and can go wrong in a number of diseases such as cancer and heart disease.

So we know that cells are responding to physical changes to their environment. But, we don’t know exactly how the cell is able to feel these mechanical signals and convert them into a response. My work is to try to determine the exact molecular events that are involved in sensing, and responding to, these mechanical signals. I am trying to work out HOW the cells use the force. This could lead to a better understanding, and treatment of, a number of associated diseases.

I particularly enjoy studying this topic because it is a very ‘new’ area of biology. For years biologists focussed on the chemical side of cell signalling; however, now we are just beginning to see the importance of this more physical-based signal interpretation. This means there is still a lot to be discovered, which makes it a very exciting field to work in. We work a lot with various biomaterials, in order to manipulate the ‘stiffness’ of the artificial environment that the cells are growing in. This uses aspects of physics and engineering and really highlights the importance of cross-collaboration between these different areas in order to fully understand the complexity of our bodies.

I also write a blog about science that we come across in our everyday lives, but is often ignored. Please check it out here: http://thatsinteresting.scienceblog.com/


Going further

As I mentioned, this is a relatively young field, so there aren’t a huge number of websites with further information that aren’t boring research papers! Here are some that I could find.

Our lab group: http://ballestremlab.com/

For general info about cell signalling: http://www.nature.com/scitable/topicpage/cell-signaling-14047077

The mechanobiology institute in Singapore has some pretty cool videos on their YouTube channel. https://www.youtube.com/channel/UCDXgKXsx2cK-662Ta6wvtEQ


 

Pondering Podocytes

by YPU Admin on June 19, 2014, Comments. Tags: biology, medicine, and Research

Introduction

My name is James McCaffrey and I am doing a medical PhD. I went straight into medical school after finishing my A-levels, and graduated in 2007. I continued my training as a junior doctor in Manchester before deciding to specialise in paediatrics in 2009. After a few years of being a paediatric doctor, I became interested in children’s kidney disease and began a PhD at the University of Manchester in 2011.

My PhD focuses on a childhood kidney disease called ‘nephrotic syndrome.’ The medication we have for treating nephrotic syndrome only works for a proportion of children, and sometimes results in unwanted side effects. No one knows exactly how this medication works. By trying to understand more about the important actions the medication has in children with nephrotic syndrome, we may be able to develop more effective drugs with fewer side effects in the future.


In Depth

What is nephrotic syndrome?

One of the main functions of the kidney is to filter the blood, so unwanted substances can be removed from the body. However, it’s also vital that the kidney filter does not let important proteins and minerals leak through. An essential part of the kidney filter is a cell called the podocyte, which keeps blood proteins in the body, while letting substances harmful to the body pass through.

In nephrotic syndrome, the podocytes become damaged and the kidney filter becomes abnormally leaky, so these important blood proteins are lost from the body. These proteins help regulate where water is stored in the body and are needed to fight infection. When they are lost in nephrotic syndrome, children have a high risk of developing serious infections and water moves from the blood into various tissues so patients develop massive body swelling. 

How is nephrotic syndrome treated?

Children with nephrotic syndrome receive an 8 week course of a type of steroid called prednisolone (this is very different to the steroids body-builders use!). Some children respond very well to this treatment, the kidney filter returns to normal, and they never have the disease again. Some children respond well initially, but the disease comes back several times over a number of years. Unfortunately, some children do not respond to steroids at all, and more powerful medications are needed. The children who do not respond to steroids during their first treatment course sometimes have long term problems with their kidney.


Why is nephrotic syndrome important?

Approximately 200 new children develop nephrotic syndrome in the UK every year. As late as the 1950’s approximately half of children with nephrotic syndrome died (mostly from infections). Although today we have more effective treatments available, children taking steroids sometimes experience unwanted drug side effects such as weight gain, high blood pressure and acne. Children who do not respond to steroids have a high chance of developing long-term kidney problems, which may ultimately require kidney transplantation.

What do I investigate?

Although steroids have been used in nephrotic syndrome for many decades, no one knows exactly how they work! It’s also unclear why some children respond well to steroids, while others do not. I mainly work on podocytes grown in the laboratory and characterise their response when they are treated with steroids. This involves finding out what new proteins are made when podocytes are treated with steroids, and investigating whether any of these may be important in the response that the kidney filter has in children with nephrotic syndrome when they receive medication.

Steroids do a lot of things: some of them helpful to the kidney barrier, and some of them unhelpful (which is why children experience side effects). If we could understand more about the helpful actions that steroids have in nephrotic syndrome, we may eventually be able to make drugs that are effective for all children with nephrotic syndrome and also have fewer side effects.

Going Further

More information about nephrotic syndrome from a patient’s perspective can be found here (http://www.nstrust.co.uk/pages/home/aboutns)

Here’s a great website for finding out about all the kidney research happening in Manchester (http://www.gmann.co.uk/website/index.cfm)

An explanation of other projects happening in my PhD supervisor’s laboratory can be found here (http://www.wellcome-matrix.org/research_groups/rachel-lennon.html)

Here are some PhD projects that doctors in the North West are currently working on (http://www.liv.ac.uk/north-west-england-mrc-fellowship-cpt/fellows)


 

Growth hormones and variations

by YPU Admin on February 28, 2014, Comments. Tags: biology, PhD, and Research

Introduction

I’m Lee Dunham, and I’m currently in the third year of my PhD research in Biomedical Science. After completing my GCSEs (many moons ago!), I went to college to study Biology, Psychology, Sport Science (A-levels) and Maths and Chemistry (AS-levels). At the time I thought I wanted to do Medicine, but changed my mind to continue into research. I got a place studying a straight Biology degree at Cardiff University. Throughout the course, I went on field courses to Tobago, and worked for a leading pharmaceutical company (AstraZeneca) and contributed to a published study. Upon graduating from Cardiff University, I started on my PhD research at the University of Manchester. My work here focusses on understanding how growth hormone, present in all humans, is regulated and how changes may contribute to differences seen between individuals.


In Depth

Why does it matter that we understand the differences? Whilst “variation is the spice of life”, we like these variations to be within a ‘normal limit’. Growth hormone (as the name suggests) controls growth and development in all mammals, and is the main cause for the variation in our heights and sizes. Some people make more of it, and others make less…

Sometimes however, the regulation fails from keeping growth hormone at a ‘normal’ level, and unfortunately this can result in disease. For example, misregulation may cause cancer, acromegaly and growth hormone deficiency. Whilst some of the characteristics of these are noticeable as being much taller or shorter, other more detrimental symptoms are also caused. These include joint pain, limited vision, headaches, increased fat mass, decreased bone density and even death.

I am aiming to identify the ‘normal’ patterns of the growth hormone gene. This gene in humans is unique to any other mammals as it has vital components allowing for stringent control. I look at single cells under a powerful microscope to observe these patterns. To make this possible, I have added a section into the growth hormone gene which makes it glow when it is present. That way, when growth hormone is being made in the cell it brightens up, and then goes dull when production stops. Each blob is a cell in a dish with my modified growth hormone gene in. Measuring the time, frequency and intensity of these events will allow me to identify ‘normal levels’ which can then be compared to different conditions.

Through both my Biology BSc and my PhD, I have learnt so many theoretical and practical skills within the laboratory. I regularly use high-tech microscopes, manipulate genes and apply a number of analytical tests. Working with some of the newest technology in a lab with people from different places and backgrounds to understand something nobody else yet knows is extremely rewarding, and I now have skills which can be transferred to many different research areas and jobs.

Going Further

Found out about studying Biology at the University of Manchester here.

For a link to the medical and human sciences page go here and you can find all the research done at University of Manchester.

And here you can find the research done specifically looking at human development.

For a great video which explains genetics and variation go here.


 

Exploring the biological clock

by YPU Admin on December 16, 2013, Comments. Tags: biology, Neuroscience, PhD, and Research

Introduction

My name is Joe and I am a final year PhD student at the University of Manchester where I study Neuroscience. Having finished my A-levels in Biology, Chemistry and History, I applied to study Zoology in Manchester.  Once accepted, I deferred the start of my degree for a year to fulfil a childhood dream to travel the length of South America while attempting to learn Spanish along the way - albeit pretty badly.

Having survived my travels, I finished my undergraduate course with a first class degree and decided to carry on my studies at Manchester through a research masters in Integrative Biology. It was during this time that I ended up on a laboratory-based project with my current supervisor and I became interested in the field of biological rhythms and their role in neurological disorders. Almost four years on, I am still focused on trying to understand how changes to your body’s biological clock within your brain can contribute to the unusual behaviour seen in bipolar disorder.






In Depth

As you have continued reading, I imagine you may be wondering what are biological clocks and what do they have to do with bipolar disorder?  As we live on a planet that rotates over a 24-hour cycle, all organisms are subjected to daily changes in light, temperature and many other factors important to life. Almost every species on earth has responded to these environmental changes with the slow evolution of biological clocks that allow us to anticipate these daily cycles. These clocks are made up of genes and proteins that strictly control the timing of cellular and body processes.


In humans and mammals, these biological clocks now exist in a deep part of our brains as two dense clusters of brain cells known as the suprachiasmatic nuclei. These tiny but intricate structures strictly control the timing of almost everything in our bodies, from when we wake up to when our hormones are released. They also they let our cells know when they need to do specific jobs at different times of the day. When these biological clocks go wrong, there is a growing amount of evidence that has shown you are much more likely to become ill.

Illnesses that have been linked to faulty body clocks are quite varied but include neuropsychiatric disorders such as depression, schizophrenia and bipolar disorder. People with these diseases very often have highly disturbed sleep-wake rhythms, often sleeping much less, or waking up a lot during the night and we think that faulty body clocks might be to blame.

My work focuses on trying to understand how molecular and electrical activity changes in the suprachiasmatic nuclei during bipolar disorder and whether any such changes in biological rhythms may contribute to disruptions in our daily behaviour. As many drugs that can change our body clocks are being rapidly discovered, we hope that this type of work will pave the way for the use of new medicines that improve body rhythms to help treat people with bipolar disorder and other similar neurological problems.

Going Further

Find out what’s going on in Manchester’s vibrant Neuroscience department here.

The University of Manchester’s Neuroscience course page, where you can find out about what you can study and what you need to do if you are interested.

Find out what type of body clock you have here and compare yourself to others around the world via this global questionnaire, set up by the world’s most prominent biological rhythm researchers:

The Guardian’s two Neuroscience blogs, with some nice articles on the most recent advances and stories in the field - click here and here.

Take a look at the British Neuroscience Association (BNA) for up-to-date news and information from the UK’s biggest Neuroscience organisation.

Only for the most intrepid minds out there! A link to the most prominent neuroscience journal out there including a weekly open-access article (you need to pay to read these normally). Don’t be put off by the crazy language as you will only really understand this after years of study, but you can get an idea of what real neuroscience looks like here.