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Pill on a String can Detect Cancer Without Need for Biopsy

last modified Dec 03, 2015 10:24 AM

July 2015

- Dr. Rebecca Fitzgeralds Group have recently published a paper in Nature Genetics wherein they describe the heterogeneity of the clonal architecture in Barrett’s oesophagus and oesophageal adenocarcinoma. Their findings strengthen support for the molecular Cytosponge technique, which overcomes sampling bias and has the capacity to reflect the entire clonal architecture. A press release based on this work and the Cytosponge technique was recently published in the Telegraph and shown below.-

 

Cambridge University has developed a quick way of testing for gullet cancer using a tiny sponge on a string.

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The pill on a string which dissolves into a sponge 
By Sarah Knapton, Science Editor
4:17PM BST 20 Jul 2015

A ‘pill on a string’ has been developed by the University of Cambridge to detect the early signs of gullet cancer without the need for a biopsy. The pill is swallowed and when the outer case dissolves it reveals a sponge which can then be pulled up the throat lining, collecting cells. Researchers say the tiny sponge is more effective at picking up cancer because it takes a swab of the whole throat and not just a small area that a biopsy would examine. Oesophageal cancer is often preceded by Barrett’s oesophagus, a condition in which cells within the lining of the oesophagus begin to change shape and can grow abnormally.

 

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When the pill dissolves it turns into a sponge.

Between one and five people in every 100 with Barrett's oesophagus go on to develop oesophageal cancer in their life-time, a form of cancer that can be difficult to treat, particularly if not caught early enough. The new test can pick up the earlier condition which means treatment can start sooner. “The trouble with Barrett’s oesophagus is that it looks bland and might span over 10cm,” said Professor Rebecca Fitzgerald, at the Medical Research Council Cancer Research Unit at the University of Cambridge. “There is a great deal of variation amongst cells. Some might carry an important mutation, but many will not. If you’re taking a biopsy, this relies on your hitting the right spot. “Using the sponge appears to remove some of this game of chance.”

The team has taken samples from 73 cancer patients over three years so that they know exactly which mutations indicate that the disease is present. They found patterns of changes where one letter of DNA had been switched for another to provide a ‘fingerprint’ of cancer.
The researchers also discovered that there appeared to be a tipping point, where a patient would go from having lots of individual mutations, but no cancer, to a situation where large pieces of genetic information were being transferred between chromosomes. Co-author Dr Caryn Ross-Innes adds: “We know very little about how you go from pre-cancer to cancer – and this is particularly the case in oesophageal cancer. “Barrett’s oesophagus and the cancer share many mutations, but we are now a step closer to understanding which are the important mutations that tip the condition over into a potentially deadly form of cancer.” The research was funded by the Medical Research Council and Cancer Research UK.

 

Professor Rebecca Fitzgerald discusses the Cytosponge technology (video).

 

Other key articles of this work were published by the Daily Mail NewsweekGizmagCambridge News , and WebMD .


Stimulating Cell Packing to Understand Human Growth

last modified Dec 01, 2015 06:10 PM

July 2015

Dr. Ben Hall has recently had his work published in Biophysical Journal, entitled: ‘Emergent Stem Cell Homeostasis in the C. elegans Germline Is Revealed by Hybrid Modeling’. Some of this work was selected as a covering image for the journal (below). In the following report, Dr. Hall discusses the rendering of this colour image and his groups innovative work with computational models of Cancer Biology.   

Stem cells are fundamental building blocks for organ growth. They are cells that have not committed to doing a specific job and, therefore, can be directed by different signals to perform a wide range of tasks. The cover image shows the shapes of stem cells while they undergo the process of organ growth, in a computational model. The cells themselves are packed tightly, and so to reduce the amount of unused space in the organ they form a hexagonal arrangement. This isn’t unique to cells; if you pack oranges or balls on a shelf tightly you can see the same kind of packing. The type of packing reflects both the shape of the cells, and the amount of crowding in their environment.

newsletterOur simulations don’t generate these images automatically. When we want to analyse this type of system we take the raw data, typically in a text file, and use a specialized tool to view it as a 3D object. We did this using the tool VMD (http://www.ks.uiuc.edu/Research/vmd/) and rendering the cells as spheres. This is a very powerful way to show how the cells move and grow and is important for many types of analysis.

For this image we wanted to generate a different kind of visualization. We wanted an image that showed the cell packing unambiguously and more closely resembled the experimental microscopy data. To do this we performed a mathematical analysis—a Voronoi decomposition—to calculate the edges of the cells. For each cell we then rendered these faces as colored blue glass and drew in a small green sphere to show the center of the cell. This clearly shows how cells in the niche pack hexagonally, and the resulting image resembles the microscopy images much more closely. This makes direct comparison much simpler and can be used to validate the simulations.

Both the cover image and our article show what can be done using detailed computational models to understand organ growth. Although the work is focused on one specific system—the germline from the nematode C. elegans—both the model and the approach may have significant impacts beyond this system. The organ structure, a stem cell niche, is found commonly in many different systems, and just as tumors may grow in the C. elegans germline, mutations may cause human stem cell niches to develop into cancers. Similarly, our group at the MRC Cancer Unit, University of Cambridge, is looking to use the same methods and tools to model different pre-cancer and cancer systems. This includes studying detailed models of individual components and large biochemical networks in cells. The Fisher group at Microsoft Research and the Department of Biochemistry, Cambridge University, is using the same computational methods to model the molecular mechanisms underlying cancer (e.g., leukaemia, glioblastoma) as well as blood development.

For information on our research, visit  the  group’s website and blog http://drhallba.wordpress.com. For information on the Fisher group, view http://research.microsoft.com/en-us/people/jfisher/ and recent press release related to their work on blood development http://research.microsoft.com/en-us/news/features/leukemia-drugs-computer-model.aspx.

– Benjamin A. Hall, Nir Piterman, Alex Hajnal, Jasmin Fisher


Cells behaving badly: researchers discover switch that may trigger cancer

last modified Dec 09, 2015 11:00 AM

June 2015

Researchers have discovered the atomic structure of a protein which controls how cells make decisions, and which may cause skin disease and predispose cells to cancer, challenging received wisdom about how it works. The new results suggest that tiny movements, on the scale of a millionth of a millimetre, effectively switch the protein on and off, driving changes in cell behaviour.

Through a large interdisciplinary collaboration funded by the Medical Research Council, Cancer Research UK, the Wellcome Trust and the Royal Society, researchers at Birkbeck, UCL and Cambridge worked together to use advanced techniques from biology, physics, and computational science to show what the protein, IKK-gamma, looks like and how it moves. From this, they proposed how it initiates different cellular behaviours.

IKK-gamma is long and flexible, and as such standard approaches such as X-ray crystallography could only show the structure of small fragments. To overcome this, the team used a magnetic resonance technique whereby molecular sized magnets were attached to the protein as labels. When placed into a strong magnetic field, pairs and quartets of these labels respond to microwaves, and allow the distances between them to be measured. By putting sets of labels in different locations in the protein the distances between different parts of the protein could be calculated. The results were then used to choose between different proposed structures until only one compatible structure remained.

Professor Chris Kay, from UCL, commented that “the study shows how powerful interdisciplinary work can be. None of the approaches on their own could give us this much insight into how IKK-gamma works.”

Dr Ben Hall, from the MRC-Cancer Unit at University of Cambridge added “Through bringing together state of the art modelling approaches with experiment we’ve been able to show how small changes may tweak the structure of the protein, which in turn leads to whole-cell and even tissue behaviour.”

This work gives an unprecedented insight into how a single protein may control large numbers of signalling networks. These findings also suggest how proteins from other biological systems with similar structures integrate information in the cell.

Commenting on the findings, which were published this month in the Journal of Biological Chemistry, Dr. Ben Hall said: “This is the most complete view of IKKG ever achieved. The combination of both the level of detail seen and the completeness of the data are the first step to thinking about how understand how IKKG goes wrong in different diseases, and how treatments may be designed in future to correct these mistakes.”

Bagnéris C, Rogala KB, Baratchian M, Zamfir V, Kunze MB, Dagles S, Pirker KF, Collins MK, Hall BA, Barrett TE, Kay CW.Probing the Solution Structure of IκB Kinase (IKK) Subunit γ and its Interaction with Kaposi's Sarcoma Associated Herpes Virus Flice Interacting Protein and IKK Subunit β by EPR Spectroscopy..J Biol Chem. 2015 May 14. pii: jbc.M114.622928. [Epub ahead of print].

 

Ikk Gamma
Figure: The solution structure of IKK-gamma (found using molecular modeling and EPR)

                                                               

 

                                                                       

 

 

 

 

 

                                                                         Video: Dr Ben Hall discusses his research. Ben_H_00015 (4)

 

Hutchison/MRC Research Centre Highly Commended at EAUC Green Gown Awards

last modified Dec 01, 2015 06:11 PM

Our building, the Hutchison/MRC Research Centre, was Highly Commended at this week's annual EAUC Green Gown Awards. Now in their 10th year, the Green Gown Awards recognise the exceptional sustainability initiatives being undertaken by universities and colleges across the UK. The Research Centre was a finalist in the Technical Innovation for Sustainability category, based on its use of demand ventiliation control (a first in the UK). This system, along with an improved environmental culture amongst all occupants of the building, has resulted in a significant reduction in gas and electricity consumption, resulting in both financial savings and reduced carbon emissions. We hope that this award facilitates the sharing of best practice with other research institutions.

For more information about the awards visit the EAUC Green Gown website.

For more information about green activities within the MRC Cancer Unit and Hutchison/MRC Research Centre visit our energy and environment pages.


MRC Cancer Unit Programme Leader Wins United European Gastroenterology (UEG) Research Prize

last modified Dec 01, 2015 06:12 PM



rcf 2014smCongratulations to our programme leader, Professor Rebecca Fitzgerald, who has been awarded this year's UEG Research Prize for her pioneering work on early detection methods for oesophageal cancer. The annual prize, worth €100,000, is awarded each year for excellence in basic science, translational, or clinical research, and researchers must also be able to demonstrate that their previous work has had an impact in its field and is recognised internationally. Rebecca's work was particularly noted for its "practical and innovative approach to important clinical problems, which maximizes the potential for successful application".

The Prize will will support a research project entitled: Combination of quantifiable genomic assays with a patient friendly non-endoscopic cell retrieval device called Cytosponge™ for management of patients with Barrett’s oesophagus. The aim of the project is to bring the biomarker research undertaken by the Fitzgerald group to routine clinical practice.

For more information visit the UEG website.