Prof. Amit Meller from the Faculty of Biomedical Engineering at the Technion, who developed an innovative method for mapping DNA molecules, collaborates with researchers from around Europe as part of the BeyondSeq consortium. The task: locating epigenetic information, which may help in the early diagnosis of cancer and other diseases
At the end of June, the international BeyondSeq consortium was inaugurated in Israel, in which the Technion, Tel Aviv University and five bodies from Great Britain, Sweden, Belgium and France are partners. The goal: to develop methods for deciphering epigenetic information from clinical samples. BeyondSeq ("Beyond Sequencing") was founded thanks to a grant of 6 million euros from "Horizon 2020" - the framework program of the European Union, which chose it and 7 other research groups out of 450 groups that submitted proposals.
"Genome sequencing is one of the most dramatic revolutions in the field of life sciences and medicine," explains Prof. Amit Meler from the Faculty of Biomedical Engineering, who heads the technical group in the consortium. "However, the existing sequencing allows mapping of the basic genomic sequence (represented by the letters A, C, G, T) but not of epigenetic information. Furthermore, DNA replication introduces errors in the sequence reading, completely erases the epigenetic information, and involves high costs. All of this is saved in our method, which also allows the use of tiny samples consisting of a few molecules." According to estimates, the method will be used for the early diagnosis of diseases and to monitor their development without the need for an invasive procedure.
Epigenetics is a branch that studies chemical change processes in the DNA bases but do not involve changing the DNA sequence. The epigenome is flexible and changes as a result of environmental influences such as nutrition and stress, and early identification of the changes that apply to it may lead to earlier and more effective treatment of diseases derived from them, including cancer.
"As epigenetic research develops, its enormous importance becomes clear, since the epigenome has many and dramatic clinical consequences," explains Prof. Meller. "Deciphering epigenetic dynamics is a huge scientific challenge, as existing sequencing methods do not reveal this information directly. This is one of the gaps that our consortium came to fill: the development of ways to read the epigenetic information along individual DNA molecules and for computerized interpretation in the clinical context, that is, the diagnosis of pathological disturbances and the first signs of bowel cancer and lung cancer."
The Meller Laboratory has developed a DNA reading technology using nanometer nozzles, which are as thick as a DNA molecule (about 2 nanometers), drilled into thin silicon layers. The DNA molecules, built as chains charged with a negative electric charge, are attracted by electromagnetic means towards the holes, and one of the ends of the chain is threaded into the nanohole with the help of the electric force. While the chain passes through the hole, a scan of the molecule is performed (by optical or electrical means).
Prof. Meller began working in the field of biophysics of single molecules during his doctorate at the Weizmann Institute of Science. After that, he studied (post-doctorate) in two laboratories: in the department of molecular genetics at the Weizmann Institute and at Harvard University in the USA (biology), where he began working on nano-nozzles. He then stayed as a senior research fellow at the Roland Institute at Harvard for 8 years, and headed the laboratory for the biophysics of single molecules. From there he moved to Boston University as a permanent associate professor in the Department of Biomedical Engineering. In 2010 Prof. Meller returned to Israel to the Faculty of Biomedical Engineering with a secondary appointment in Biology, and is a member of the Russell Berry Institute for Nanotechnology.
The technology that will be developed as part of the BeyondSeq consortium was developed by Prof. Meller as early as 1998 at Harvard University, and now the task is to adapt it from "normal" sequencing to epigenetic sequencing. This year the group has already published three scientific articles on this topic: improving the optical nanonozzle detector (Nano Letters, 15, 745-752, 2015), identification of individual ubiquitin proteins by nanonozzles (Biophysical Journal 108, 2340-2349, 2015) , and mapping of transcription factors along DNA at the single molecule level (Scientific Reports 5, 1-11, 2015).
"The research in my laboratory has always been on the seam between basic science and its applied aspects - and in this case in the fields of clinical sequencing and personalized medicine. In the USA we developed new methods for sequencing DNA molecules with funding from the American Institute of Health (NIH). The goal of the project, which I joined when it was established in 2005, was to lower the cost of genome sequencing by about 5 orders of magnitude. When I joined the program, the cost of sequencing the human genome was more than ten million dollars (for the genome of a single person) - an amount that only a few can afford. Today, largely thanks to the NIH project, such flooring costs less than a thousand dollars and is beginning to enter health care baskets around the world. This revolution, which occurred as a result of the development of completely new tiling methods - and not just the perfection of existing methods - has dramatic consequences for basic research, for medicine and for the society in which we live."
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The beauty of this project, similar to others, is the attempt to deal with the biggest problems of science and medicine by methods whose essence is the examination of each molecule on its own, in contrast to most methods that tend to look at everything together. It's a bit like identifying if someone has arrived at work by counting all the employees in an office building at a given moment instead of looking for them on the security camera at the entrance to the building.
When the difference between the methods is the level of influence of additional factors on the answer obtained, while in the first method any excess or lack of another person can lead to a wrong conclusion, by looking at the camera there is no examination of each worker against himself, therefore the chance of mistakes decreases significantly, this makes the dangers specific And the type of information you get is different.
Therefore, the technological limitations are fundamentally different and many problems that the standard methods have no easy/cheap way to solve are possible with these kinds of technologies.
The benefits are many, even if we try to look at existing additions to a known molecule such as epigenetic information on DNA as in the above article. And also based on prior knowledge it is possible to specifically mark what you are looking for and then find it specifically the marking.
The world is moving towards personalized medicine, these technologies are just another entanglement in the perceptual transition that specific knowledge about the patient and his specific problems is needed for the nation that exists today that compares the problems of a patient to the average problems of his age group.
Yossi, blood tests also have potentially bad consequences, so do talkbacks and people who call them miracles. Knowledge is a power that needs to be defined and then we can use it for the benefit of humanity and not for its detriment. What is the good of humanity? Does not knowing exempt us from the need to investigate? In fact, our hope depends on the legislative committee that will be established, I hope that there will not be people who choose to state the obvious.
Joseph
There is a simple solution to this. In the US, the medical insurance companies are allowed to ask two questions - age, and whether you smoke.
This important invention also has potentially bad consequences. If insurance companies can conclude from one blood test that we will be sick with disease X within Y years, they may refuse to insure us, or at least bargain with us so that we are not insured for a certain disease. The difference from now is that they don't know who will get sick with what, and by applying this science, they will know. Every scientific development should be accompanied by a social/cultural development that will be ready to accept this knowledge in a configuration that will do good to people and not bad.