{"id":4979,"date":"2015-08-24T12:34:29","date_gmt":"2015-08-24T10:34:29","guid":{"rendered":"http:\/\/news.embl.de\/?p=4979"},"modified":"2024-04-19T15:21:12","modified_gmt":"2024-04-19T13:21:12","slug":"1508-miroculus","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/alumni\/1508-miroculus\/","title":{"rendered":"Decoding disease"},"content":{"rendered":"\n

\u201cEverything started with a dream,\u201d says Alejandro Tocigl, an entrepreneur from Chile and CEO of Miroculus, a start-up company aiming to \u2018democratise\u2019 molecular diagnostics with a tool that could enable patients to be checked for diseases in a simple and affordable way, using just a millilitre of blood. His goal is clear: \u201cTo improve early diagnosis, to monitor diseases on a constant basis, and for this to be available to everyone, wherever they are in the world.\u201d Like Tocigl, most of the other founders of Miroculus are also from emerging economies and they are acutely aware of the lack of purchasing power of these countries, especially when it comes to what they call \u2018medicine for the masses\u2019. \u201cWe want this tool to be available to all of them,\u201d says Tocigl. \u201cWe don\u2019t want to discriminate based on socio-economic status.\u201d<\/p>\n\n\n\n

Miroculus\u2019 chief scientific officer is EMBL alumna Fay Christodoulou, an expert on microRNAs, which form the basis of the company\u2019s technology. She first met Tocigl and the rest of Miroculus\u2019 founding team in 2013 during a ten-week graduate studies programme at Singularity University, a California Benefit Corporation located at NASA Research Park in Silicon Valley, which offers programmes and activities that encourage the use of technology for change. Its graduate programme attracts individuals from a broad spectrum of disciplines and encourages them to pursue an ambitious goal: to develop an idea and a viable business plan that harnesses exponential technologies to positively impact one billion people within ten years. Christodoulou teamed up with Tocigl together with Pablo Olivares, a doctor also from Chile; Gilad Gome, a biotechnologist from Israel; Ferr\u00e1n Galindo, an entrepreneur from Panama; and Jorge Soto, a Mexican electronic engineer. The six of them struck on the idea to develop a simple blood test that utilises the potential of microRNAs in the bloodstream as highly sensitive biomarkers for disease detection.<\/p>\n\n\n\n

\"mir.i.am
mir.i.am is a microRNA detection platform designed for molecular data gathering, analysis and interpretation. PHOTO: Miroculus<\/figcaption><\/figure><\/div>\n\n\n\n

Bright biomarkers<\/h3>\n\n\n\n

MicroRNAs are small pieces of RNA that regulate gene expression, the building of proteins from the information encoded in DNA. First discovered in 1993, a relationship between microRNA dysregulation and cancer was reported in 2002. Six years later, researchers found that microRNAs circulate in biological fluids like blood, which makes them promising biomarkers for the early stages of cancer, heart disease and neurological diseases. The detection of specific microRNAs in a sample makes it possible to diagnose a disease, identify its type (each tumour, for example, has its own microRNA signature), and monitor its progression and treatment in minimally invasive ways. However, techniques involving microRNAs are challenging because these molecules are no more than 22 nucleotides long and cannot easily be detected with traditional DNA-based methods. Moreover, they are often very similar: two microRNAs may share all but one nucleotide. Hence, methods for their detection and classification need to be able to tell two microRNAs apart based on very small variances.<\/p>\n\n\n\n

Miroculus can potentially offer a disease agnostic screening test which simply interprets the microRNA signatures that are found<\/p><\/blockquote>\n\n\n\n

Christodoulou\u2019s expert knowledge of microRNAs stems from years of research in the field. She completed her doctoral thesis on ancient animal microRNAs at EMBL in 2010 and investigated the role of microRNAs in thyroid cancer during her postdoctoral research. \u201cI have been following the field since 2005 and I am very familiar with the technologies that are available,\u201d she says. \u201cWhen I think of what we are doing, something like this is definitely missing.\u201d What they are doing is building \u2013 and perfecting \u2013 a device that scans for diseases quickly, easily and affordably. Miroculus\u2019 method extracts the microRNAs from a standard blood sample and these are then pipetted into a 96-well plastic plate. Each well is filled with the company\u2019s patented biochemical assay that produces a fluorescent signal in the presence of a specific microRNA. To run the assay, the plate is placed inside the device \u2013 called mir.i.am \u2013 which can be connected to a smartphone. The phone takes photographs during the reaction and sends them to a cloud where the pattern of illuminated wells is matched against data on which disease is associated with which microRNA pattern. \u201cIt is the combination of specific microRNAs found in a sample which can reveal the source of a pathophysiological condition,\u201d explains Christodoulou. \u201cBy providing an affordable and easy to use platform that can \u2018read\u2019 which microRNAs circulate in a sample, Miroculus can potentially offer a disease agnostic screening test which simply interprets the microRNA signatures that are found.\u201d Thus, whereas other diagnostic tests look for a specific disease, Miroculus\u2019 method could be applied to multiple disease types.<\/p>\n\n\n\n

Design to development<\/h3>\n\n\n\n

Although, as Christodoulou points out, the clinical validity and utility of microRNAs as biomarkers has so far only been established for some cancers and cardiological conditions, Miroculus\u2019 team believe that their various advantages over other biomarkers mean that they have great potential for early disease detection. These advantages include the stability of microRNAs in plasma, which stops them from degrading easily even when stored at room temperature, and their high cell-type specificity. As certain microRNAs are only found in certain cells, the assay reveals which cells are present in a given sample. In tests, the team has been able to identify the microRNA patterns indicative of pancreatic cancer, breast cancer and hepatic cancer.<\/p>\n\n\n\n

\u201cWe want to provide the enabling technology that can establish their use,\u201d says Christodoulou. Yet for Miroculus, simply providing that technology isn\u2019t enough. \u201cAfter learning how important design thinking is in product development,\u201d Christodoulou recalls, \u201cwe follow a different approach to stereotypical spin-offs that have a very good assay or a very good biotechnological solution and then want to make it available as it is.\u201d Rather than simply providing a solution that can only be used under very specific conditions or by experts, the team wants to make the technology available as cheaply as possible to be used by minimally trained lab technicians in low-resource settings. The first two prototype versions of the mir.i.am, Christodoulou explains, were 3D-printed, using cheap, off-the-shelf components, which would make it possible for the device to be reproduced relatively easily.<\/p>\n\n\n\n

GeneCore groundwork<\/h3>\n\n\n\n

As the development of the project began to take flight, Christodoulou conducted instrumental research at EMBL\u2019s Genomics Core Facility<\/a> (GeneCore), which has been run by Vladimir Benes, a trained biochemist, since its inception in 2000. Christodoulou worked closely with Benes for many years, and since leaving EMBL she keeps returning as a regular tutor on a small-RNA analysis course he organises. Thus, when the Miroculus team realised that they needed to find a place where they could continue the experiments they had begun at Singularity University, Christodoulou\u2019s mind quickly settled on GeneCore, which she describes as \u201ca paradise with all the toys a molecular biologist could dream of. The lab is fully equipped with everything and runs like a Swiss watch,\u201d she explains. \u201cWe literally turned up there with our suitcases and started pipetting.\u201d<\/p>\n\n\n\n

\"Fay
Fay Christodoulou is now based in San Francisco. PHOTO: Fay Christodoulou<\/figcaption><\/figure><\/div>\n\n\n\n

EMBL had never hosted a start-up before but Benes explains that Christodoulou\u2019s tenacity, motivation and commitment convinced him that she would be able to sustain the project, even during its challenging phases. \u201cSo when she asked me if we could do this research together, my immediate thought was: \u2018Let\u2019s do it!\u2019\u201d, he recalls. One such challenge occurred when Christodoulou had to significantly alter her scientific approach on realising that the original design of their isothermal assay had reached its limits: not all microRNAs would perform similarly at the same temperature. She praises the support of the team at GeneCore, with Miroculus staff scientist Jo\u00e3o Pereira de Lima based at the facility for six months to manage the project. \u201cWorking together we were able to deliver detailed analyses of individual parameters and components that provided robust data for Fay to present to investors,\u201d explains Benes.<\/p>\n\n\n\n

Setting up shop<\/h3>\n\n\n\n

When Miroculus advanced from a part-time venture to a stage where the project needed the team\u2019s full attention and additional resources, the data produced at EMBL enabled the start-up to secure the funding for the first prototype, which was introduced at a TED global conference last year. This was followed by 25 days of touring the US, pitching it to almost 100 investors \u2013 a particular challenge for a company that did not yet have facilities in the country. Miroculus completed the first round of seed funding this year. The company is now based in San Francisco, focusing on optimising the product\u2019s workflow and user experience, while making the assay more robust so that it can tolerate inexpert handling and still produce accurate results. Silicon Valley, with its infinite, revolutionary ideas, excellence, and easy-access expertise has a lot to offer, says Christodoulou: \u201cIt is a very fertile environment for developing solutions that have the potential to make a real difference in the world\u2026 to where they could never be found before.\u201d EMBL, she insists, is its European equivalent in the life sciences.<\/p>\n\n\n\n

Bold innovation is about bringing forward the change you want to see in the world.<\/p><\/blockquote>\n\n\n\n

Although the notion of leaving academia to pursue an entrepreneurial dream may seem daunting to some, Christodoulou and the others involved in Miroculus are an example of what interdisciplinary teamwork can achieve. To other researchers who \u2018flirt\u2019 with the idea of trying out their entrepreneurial skills, Christodoulou has a clear message: \u201cGo for it and don\u2019t be afraid of failure. Bold innovation is about bringing forward the change you want to see in the world.\u201d<\/p>\n\n\n\n

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