Sunday, 30 November 2014

30 days of Movember

I look ridiculous. It itches, and the majority of the comments I've received can't be repeated here. Nevertheless, I've survived 30 days of Movember; summed up in this video:


And all for a good cause. In 2012 alone, over 307,000 people were estimated to have died from prostate cancer. 30 die a day in the UK alone. Whereas the main risk factor for prostate cancer is age, testicular cancer is the most common cancer in men aged 25-49 in the UK. Luckily, cure rates are far higher with this form. Regardless, there is still far more that can be done. Please support this good cause on my Movember page here. Thank you to everyone that's done so already.

If you're interested, more cancer stats and info can be found on CRUK's webpage here.

Sunday, 16 November 2014

Saturday, 8 November 2014

1 week in...

Thanks to everyone who's donated so far. We've raised $161 already (!) and I haven't even really grown anything yet. It's only going to get worse as well. Facial hair really doesn't suit me, so the worse I look, the more you should donate! Please carry on supporting this great cause (prostate cancer, not my face). Thanks so much!
1 week and it's starting to grow...

Saturday, 1 November 2014

Movember

This year I've decided to take part in Movember. For those still on dial-up, Movember is the annual ritual of growing a mustache over the 30 days of November. The idea is to try and raise funds and awareness of the issues surrounding prostate cancer, testicular cancer and men's mental health. In the imaging world, prostate cancer is a difficult one. We just don't have the right tools for the job. Whilst most men will die with, rather than of prostate cancer, there is a small, but significant proportion of aggressive prostate cancer that requires urgent treatment. The problem is knowing what type of prostate cancer you have. The solution is to remove the cancer by surgery - but this comes with major risk of damaging the near-by nerves, which can result in erectile disfunction and incontinence. So we don't want to remove all prostate cancers that are diagnosed. Imaging could play a great role in distinguishing the nasty from the not-so-nasty cancer. I hope we will have some success in developing such a test in my lifetime, but these things are harder to do in practise and the research is costly. So I'm going to look stupid for a month and talk to people I don't know about why we should be botherd about prostate cancer. And if you are bothered too, please donate on my Movember page here! They are already funding some great research by my fellow imaging scientists over at John's Hopkins: https://www.youtube.com/watch?v=SVWh2eHNSzo. Thanks.
Me. Day 1: 1st November 2014.

Sunday, 27 July 2014

Measuring fat breakdown to detect cancer

Last year I moved to the United States to take up a postdoctoral position at Stanford University in the lab of Prof. Sanjiv Sam Gambhir. I'm lucky enough to work in a very creative environment, nicely summed-up in this video. Living in the US however has brought some challenges I've been ill-equipped to deal with. Namely, how to avoid getting run over when crossing a road (walking seems to be prohibited here) and what to do to stop getting fat. High fructose corn syrup is added to pretty much everything and it costs nearly the same amount to eat out as to buy the constituent ingredients (eating out is cheap!). I don't stand much of a chance. Running across the road however may solve both issues.

Given my rapidly-expanding waistline, it seems pretty appropriate that my research during my last year at Imperial College London focused on measuring the breakdown of fat by cancer cells. As I mentioned in my last blog, cancer cells take up more glucose for energy production and storage. Additionally, tumours require increased levels of fat to make new cells and to create even more energy. The breakdown of fats at high rates to produce this energy sets cancer cells apart from most normal 'healthy' tissue. We have recently shown that by imaging fat breakdown, we can detect breast, prostate and brain cancer in preclinical (non-human) models, published this month in The Journal of Nuclear Medicine. This is important as existing techniques to identify and diagnose both brain and prostate cancer are not effective in all cases. Further tests, such as the one proposed in this research article, may provide additional information and eliminate the need for an invasive biopsy. By accurately detecting these cancers at an early stage, the chances of survival are greatly improved. We're still some way off evaluating this diagnostic test in patients, but I have high hopes for this new imaging technique, an example of which is shown below:

video

In other cool news this week, my academic mentor at Stanford, Prof. Sanjiv Sam Gambhir, is partnering with Google's secret research division, Google [x] - the division that's brought us Google Glass and those internet balloons. The idea behind this project, named Baseline, is to define and thoroughly characterise the genetic and molecular make-up of healthy adults (initially from 175 people, increasing to many thousands). By understanding the key features of good health, it's hoped that we may be better placed to understand and detect things that go wrong. Details of this project are light on the ground, but it's thought that some cool wearables, such as the 'smart contact lense', will be used to monitor those enrolled in the project 24/7. Let's hope this ambitious project results in a major scientific breakthrough.

Sunday, 9 March 2014

Cancer's sweet tooth

Otto Warburg
One of the best things about being a scientist is discovering something no one has ever done or seen before. Whether it be the creation of a new man-made plastic, or the discovery of the Higgs boson, science is tirelessly expanding our collective knowledge. Sometimes however, we're so busy focusing on the horizon and the next scientific breakthrough that we forget to look over our shoulder and examine in sufficient detail what has come before.

Cancer detection through imaging
A German scientist, Otto Warburg made the discovery in the 1920s that cancer cells consume sugar in far greater amounts than normal healthy cells.  It's only recently though that we have started to use this discovery to our advantage.  By designing drugs that curtail this 'addiction' to sugar it is hoped that we can stop these cancer cells from growing. We also take advantage of cancer's sweet tooth during diagnosis. Following injection of a radioactive sugar into the bloodstream, clinicians can detect cancer using a scan that measures where that sugar is being used in the body.  An example is shown to the left, with the tumour indicated by the arrow.  It is now thought that cancer cells use the sugar to protect against harmful waste products, for energy, and to create building blocks to form new cells.

Following in the footsteps of Warburg, a team of French scientists made the discovery in the late 70s/early 80s that cancer cells save some of this sugar for a rainy day - when extra energy is needed, or to keep the cells alive when the supply of sugars from elsewhere runs out. This discovery is fascinating given that sugar stores are normally only found in the liver and muscle. Cancer cells that originate from say the breast or ovary seem to acquire the ability to store these sugars through, as of yet, unknown mechanisms. These findings have been largely ignored until now. In a research article published this month in Cancer Research, myself and my colleagues at Imperial College London further explore this phenomenon, some 30 years later.  We showed that cancer cells store more sugar when they stop growing and that we can detect these sugar stores through imaging. A picture of these sugar stores are shown below, indicated by the intense orange/yellow dots within the cancer cells. The identification of these stores has wider implications as cancer cells that grow more slowly are typically more resistant to traditional chemotherapy. It's hoped that this new imaging method might be able to detect these slower growing cells that we can then target with different drugs. Although this technique hasn't been tested in humans yet, we are hoping scans, similar to the one shown above, will be performed in the next few years.  There is also hope that this technique can be used to detect other sugar storage diseases such as diabetes.
Cancer's sugar stores

For more information, the research article, 'A Novel Radiotracer to Image Glycogen Metabolism in Tumors by Positron Emission Tomography' can be found here.

Monday, 22 October 2012

The smallest detail sometimes makes the biggest difference

This latest post comes courtesy of my great friend and fellow scientist, Dr Peter Canning.  We were lab partners at the University of Warwick some 10 years ago and were always the last to leave the lab - mostly because I was so slow!  Having completed his PhD in Structural Biology at Warwick, he is now working as a postdoc for the Structural Genomics Consortium at Oxford University... 



The smallest detail sometimes makes the biggest difference 

Looking at how two molecules "talk" to each other may provide the basis for new cancer treatments


The science of cancer imaging encompasses a wide range of different techniques and disciplines. Imaging technologies allow cancerous cells to be detected, characterized and monitored, or using different kinds of imaging methods, much smaller, molecular-scale events can be observed. In every cell of the human body, millions of times a second, biological molecules signal to one another, create things, destroy things, transport things and carry out thousands of individual tasks needed to keep a cell running. Various factors can cause these highly organised processes to break down, causing the cell to malfunction. These are the kinds of malfunctions that lead to the development of cancers and indeed other diseases.

Fortunately, cells come with a range of quality control mechanisms built in. They are capable of fixing all kinds of damage, or if the damage is too severe, they are even capable of activating a kind of self-destruct mechanism that destroys the cell before the problem gets too severe. Of course, the mechanism to control the self-destruct system is carefully controlled and monitored.

One molecule involved in the control of the self-destruct sequence is called p53, in fact it is more or less the control hub, the big red button. If a cell is damaged and on the path to becoming cancerous, p53 is activated and either shuts the cell down or destroys it for good. It has been a subject of great interest for some time to biologists, because in the vast majority of cancer cells, p53 itself has become damaged and is no longer able to destroy the damaged cells. For some unknown reason, p53 has evolved to be very fragile, and so damage to p53 happens all too easily. With this in mind, scientists are working to find ways to reactivate damaged p53, or alternatively to find a way to trigger the same response that p53 would normally activate, hitting the self-destruct button for the cancerous cells and causing them to destroy themselves.


Under normal conditions (a), when a cell detects that it is damaged, a signal is sent to p53, which activates a kind of "self destruct" mechanism to destroy the cell before it can do too much damage. If p53 malfunctions (b) then it is unable to trigger this response and cells are allowed to become cancerous, growing and multiplying unchecked.























I am currently a Postdoctoral Research Associate at the Structural Genomics Consortium (SGC), at the 
University of Oxford, in the Growth Factor Signaling Group (www.thesgc.org). The SGC is a not-for-profit organization with labs in Oxford and Toronto which looks to investigate biological molecules (proteins) involved in various diseases and study them on the atomic level using an imaging technique called X-ray crystallography, then put the information into the public domain free of charge. This enables further research by the global scientific community, in particular speeding up the lengthy and expensive process of discovering new drugs.

In a paper published in the Journal of Molecular Biology this month, we use X-ray crystallography to image a communication between two molecules at the the atomic level. We wanted to address the idea of self-destructing a cell in which p53 has failed and to do this we looked at a protein very closely related to p53 called p73. p73 is capable of standing in for p53 and destroying a bad cell, with the added bonus that it is far less fragile, but for some reason this is not a common occurrence in the course of normal cellular events. In our paper we not only look at the molecular structure of p73 and how it is subtly different to p53, but also how p73 is activated. We revealed that a protein known to activate both p53 and p73 called ASPP2 activates p73 in almost exactly the same way as p53. This finding raises some interesting questions. For instance, if the system of activation targets both proteins in the same way then how is one protein chosen over the other? However, it also provides useful information for scientists looking to find a way to get p73 to switch on, stand in for p53 and destroy cancerous cells.

These types of images are used to represent the molecular structure of proteins. Here, the ASPP2 protein molecule (red) is shown interacting with both the p73 protein (yellow) and the p53 protein (blue) in an almost identical fashion. 

If you’re interested, the paper is now available from the Journal of Molecular Biology’s website:

Or you can read more about the group’s activities on the SGC’s website: http://www.thesgc.org/scientists/groups/oxford/growth-factor-signalling