BreakThrough Digest Medical News |
- An open platform revolutionizes biomedical-image processing
- Research yields two ‘firsts’ regarding protein crucial to human cardiac function
- BUSM researchers find potential key to halt progression, reverse damage from emphysema
| An open platform revolutionizes biomedical-image processing Posted: 30 Aug 2012 09:00 PM PDT
Ignacio Arganda, a young researcher from San Sebastián de los Reyes (Madrid) working for the Massachusetts Institute of Technology (MIT) is one of the driving forces behind Fiji, an open source platform that allows for application sharing as a way of improving biomedical-image processing. Arganda explains to SINC that Fiji, which has enjoyed the voluntary collaboration of some 20 developers from all over the world, has become a de facto standard that assists laboratories and microscope companies in their development of more precise products.
Ignacio Arganda is a postdoctoral researcher at the Laboratory of Computational Neuroscience of the Massachusetts Institute of Technology (MIT). Along with a group of researchers he implemented Fiji, a platform that allows for applications to be shared in order to improve and advance in the processing and analysis of biomedical imaging. “All of this in open source,” outlines Arganda. The platform was built from a previous one, ImageJ, which was well known in the industry at the time. ImageJ was not an open source platform but it was publicly accessible. According to Arganda, it had the advantage that any person working in medical imaging could easily create small software applications to resolve their particular problems and then incorporate it into the platform by means of a plug-in (an application which is linked to another providing a new or specific function). Nonetheless, the researcher adds that this platform became too chaotic with applications of all kinds, some of which were not related to biomedical-imaging. It also began being used to handle astronomical images, in video tracking, etc. “There was a significant lack of control and structure,” he says. Therefore, “in a spontaneous manner and without any help” this group of researchers decided to create the new open source platform that could put order to that already in place, reusing what was of interest and useful in their work. “We created a webpage organised like Wikipedia where people could contribute and use their knowledge to help others. To our surprise, it became very popular,” he ensures. According to Ignacio Aranda, Fiji currently has 127,000 unique visits (20,000 each month). The de facto standard “The users of the platform with their contributions are a great attribute and this drives others to share their source code. Therefore, Fiji has become a de facto standard in the biomedical-imaging sector” outlines Arganda. “This was our objective because the majority of those that participate in this project have been working for years in the field of medical imaging and we found ourselves too frequently faced with articles making reference to a fantastic method for processing images. In the end though, it was not possible to verify whether or not it was true because the technique was associated with software that was not provided and some images were not even accessible.” At the moment there are 20 developers across the whole world who are working voluntarily on improving the platform. “All of them are scientists who are working on their own projects and use the platform because it is more comfortable and they find it more interesting,” adds Arganda. The scientists behind Fiji got in contact with Arganda because of his doctoral thesis. “I was working on a project involving the study of mammary gland development and breast cancer in mice and I had a few tissue samples. I began to develop a programme for elastic image alignment that would allow me to create a 3D reconstruction. They expressed their interest and called asking me to collaborate in the platform.” In the eyes of the researcher, this is an example of what lies within Fiji. Arganda now works on automatic learning systems aimed at recognising the edges of neurons from electronic microscope images in the MIT Laboratory of Computational Neuroscience. The developed applications have also been introduced into the platform. A success amongst companies The researcher believes that the success of Fiji is also changing the way that biomedical-imaging companies are behaving. These include microscope firms with large laboratories. “These companies recognise the platform as a high quality standard and they are aware of their two options: either compete or collaborate with Fiji. They can create and maintain their own plug-in that works in the platform and they can then sell them if they become very specific. “In my case for example, I was contacted by a microscope company because they were using my elastic image alignment programme to correct deformations in their microscopes. They asked me for a specific version of the programme, but I had developed it during my thesis so it could not be sold easily. In the end we reached an agreement for its use under the one condition that they would communicate any improvement made so that it could be introduced as open-source and uploaded onto the platform. Ignacio Arganda explains that, like him, there are other researchers that have also been contacted by companies and contracted as consultants on a day-to-day basis to maintain the code necessary to develop their products. “The platform makes you highly visible,” concludes the researcher. “They offered me the chance to complete a postdoctoral fellowship at the University of Stanford and the MIT because they had access to my code for the elastic alignment software and knew what it was capable of.” In the Connectome Project with Sebastian Seung Ignacio Arganda is currently completing his postdoctoral fellowship in the MIT Laboratory of Computational Neuroscience under the supervision of the well known scientist Sebastian Seung, one of the leaders of the Connectome Project. This initiative aims to create a map of all the brain’s neuron connections using an online application called eyewire.org, which is open to public participation. Arganda is in charge of developing artificial intelligence programmes that automatically recognise neuron’s edges and are then able to reconstruct wiring in the brain. ### References: Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, Preibisch S, Rueden C, Saalfeld S, Schmid B, Tinevez JY, White DJ, Hartenstein V, Eliceiri K, Tomancak P, Cardona A. “Fiji: an open-source platform for biological-image analysis”. Nat Methods. 2012 Jun 28;9(7):676-82. doi: 10.1038/nmeth.2019 Contact: SINC |
| Research yields two ‘firsts’ regarding protein crucial to human cardiac function Posted: 30 Aug 2012 09:00 PM PDT
Using an imaging method called atomic force microscopy, Loong achieved two “firsts”: the first direct imaging of individual alpha-tropomyosin molecules, which are very small ? roughly 40 nanometers long ? and the first demonstrated examples of a measure of the human cardiac protein’s flexibility. From there, he established a baseline of how flexible a normal version of the protein is supposed to be in a healthy human heart. “This basic research is important to broadening our understanding of how the human heart functions normally at the molecular level,” Loong said. “The flexibility of alpha-tropomyosin dictates how effectively or properly the heart muscle will contract on each beat and has implications for keeping the heart free of cardiovascular disease. “Before this study, we did not know how flexible this protein was,” Loong said. “Using these results, now we can conduct subsequent studies to compare disease-related mutants of this protein to see how much they deviate from normal versions.” Loong served as the lead author of the paper “Persistence Length of Human Cardiac a-Tropomyosin Measured by Single Molecule Direct Probe Microscopy,” which was published in the journal PLoS ONE. He conducted the research with physics Professor Huan-Xiang Zhou and biological science Professor P. Bryant Chase, both of Florida State. When an electrical signal is generated in the heart to make it contract, calcium is released inside each heart muscle cell. The calcium then binds to a protein called troponin, and that triggers the “flexing movement” of alpha-tropomyosin, which allows another protein called myosin ? the motor protein ? to interact with the troponin/tropomyosin actin filaments. This series of events is what generates the heart’s contraction that pumps blood. A subsequent removal of calcium inside each heart cell is what relaxes the heart, which allows the heart to fill with blood to be pumped on the next beat. “Alpha-tropomyosin is a key element that makes the calcium signal either turn the heart on, making it contract, or turn it off, making it relax,” Chase said. “There is an optimal range of flexibility of alpha-tropomyosin for the normal heart to function properly. The molecule can be too stiff or it can be too flexible, either of which could lead to cardiovascular disease. What we ultimately think is that evolution has tuned the mechanical properties of these proteins for optimal function in the heart.” Contact: P. Bryant Chase |
| BUSM researchers find potential key to halt progression, reverse damage from emphysema Posted: 30 Aug 2012 09:00 PM PDT
A study led by researchers at Boston University School of Medicine (BUSM) has shown that a compound used in some skin creams may halt the progression of emphysema and reverse some of the damage caused by the disease. When the compound Gly-His-Lys (GHK) was applied to lung cells from patients with emphysema, normal gene activity in altered cells was restored and damaged aspects of cellular function were repaired.
The study, which is published in BioMed Central’s open access journal Genome Medicine, also demonstrates the potential impact of using genomic technologies to identify new possible treatments for diseases using existing drugs and compounds. Chronic obstructive pulmonary disease (COPD) is a chronic, progressive lung disease that comprises emphysema, small airway obstruction and/or chronic bronchitis leading to the loss of lung function. Tobacco smoke and other irritants cause oxidative stress and chronic inflammation, which over time destroys lung alveolar cells and results in emphysema. Without these cells, the lungs are not able to efficiently exchange oxygen for carbon dioxide, causing shortness of breath and low blood oxygen levels. According to the National Institutes of Health’s National Heart, Lung and Blood Institute (NHLBI), COPD is the third leading cause of death in the United States and results in approximately 120,000 deaths each year. While there are treatments and lifestyle changes that can help people cope with COPD, there currently is no cure and there are no effective therapies to reduce the rate of lung function decline that occurs as the disease progresses. “Given the high costs, both direct and indirect, associated with COPD, there is an urgent need to identify novel approaches to treat the disease,” said Avrum Spira, MD, MSc, Alexander Graham Bell professor of medicine and chief of the division of computational biomedicine at BUSM, who was one of the study’s senior leaders. Spira also is a physician in the pulmonary, critical care and allergy department at Boston Medical Center. Researchers took cells from lungs donated by patients undergoing a double lung transplant because their lungs were irrevocably damaged by COPD and found 127 genes had changes in activity as disease severity increased within the lung. The genes that showed increased activity included several that are associated with inflammation, such as those involved in signalling to B-cells (the immune system cells that make antibodies). In contrast, the genes involved in maintaining cellular structure and normal cellular function, along with the growth factors TGF? and VEGF, were down-regulated and showed decreased activity. Genes that control the ability of the cells to stick together (cell adhesion), produce the protein matrix that normally surrounds the cells and promote the normal association between lung cells and blood vessels were among the genes in this category. Using genomic technologies and computational methods, the researchers identified genetic activity defects that occur as emphysema progresses and matched these defects with compounds that could reverse the damage. “Our study results showed that the way genes were affected by the compound GHK, a drug identified in the 1970s, was the complete opposite of the pattern we had seen in the cells damaged by emphysema,” said Marc Lenburg, PhD, associate professor in computational biomedicine and bioinformatics at BUSM and one of the study’s senior authors. “What got us especially excited was that previous studies had shown that GHK could accelerate wound repair when applied to the skin,” said Joshua Campbell, PhD, a post-doctoral fellow working with Spira and Lenburg who served as the study’s first author. “This made us think that GHK could have potential as a therapy for COPD.” “When we tested GHK on cells from the damaged lungs of smokers with COPD, we saw an improvement in the structure of their actin cytoskeleton and in cell adhesion, especially to collagen,” said James Hogg, MD, from the University of British Columbia and one of the study’s senior authors. “GHK also restored the ability of cells to reorganize themselves to repair wounds and construct the contractile filaments essential for alveolar tissue repair.” GHK is a natural peptide found in human plasma, but the amount present decreases with age. While more testing needs to be done on its effects in COPD, these early results are very promising. Therapeutic studies with GHK in animal models of COPD are now underway with the ultimate goal of moving this compound into clinical trials. As more gene activity signatures are discovered, this method of matching drug to disease may provide a rapid method for discovering potential uses for existing drugs and compounds. “Beyond the identification of a potential new COPD drug, the research team developed a cost-effective approach to study COPD at the molecular level across the entire lung, and then screen potential drug candidates,” said James Kiley, PhD, director of the NHLBI’s Division of Lung Diseases, who supported this work. “This work demonstrates the potential of using genomics data to drive clinical research.” ### Research reported in this published article was supported by the NHLBI under award number R01 HL095388 and through the National Institutes of Health under award number UL1 TR000157 (Boston University Clinical and Translational Science Institute). Researchers from the University of British Columbia, the University Medical Center Groningen and the University of Pennsylvania also collaborated on this study. *Some material included in this press release was excerpted from Genome Medicine‘s press release: http://www.biomedcentral.com/presscenter/pressreleases/20120831a Contact: Jenny Eriksen |
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