The hackers teaching old DNA sequencers new tricks

The hackers teaching old DNA sequencers new tricks

In a basement storeroom at Stanford University in California, the guts of a dozen DNA sequencers have been uncovered – cameras and lasers, optics and fluid controllers worth hundreds of thousands of dollars, all cleaned up with a late-model, next-generation Illumina DNA sequencer is. Called GAIIx. On the floor, the shell of an old instrument sits empty, raised like a dead body. “I sound like a hoarder,” says Stanford biophysicist William Greenleaf.

But over the past 6 years, the collection has fueled an effort that has involved nearly half of Greenleaf’s 18-member lab team. While most researchers use DNA sequencers to sequence, well, DNA, Greenleaf’s team is one of a small number that has repurposed the tools for an entirely different goal: macromolecular interactions and proteins on a larger scale from RNA and protein. Folding for enzyme function to study nucleic-acid biochemistry.

“It’s a revolutionary technology,” says Stanford biochemist Dan Herschlag, who uses it to study the interactions between RNA and other molecules.

This provides “deep and comprehensive quantitative information,” he says, “which allows researchers to build more accurate biophysical and cellular models for molecular interactions, and which leads to a truly predictive understanding of biological systems.” An important step in that direction”.

Broadly speaking, the work demonstrates what is possible when scientists look at the guts of their hardware – evidence that the device isn’t necessarily because it’s old or out of date.

But there’s a reason this kind of technology development is called the bleeding edge: Things often go wrong. Sarah Denny, a biophysicist who graduated from Greenleaf’s lab this year, asked whether her devices offer ‘plug-and-play’ simplicity.

“Many times after you’ve done an experiment, something will break and you have to figure out how to make it work again,” she says. But considering the amount of data she could extract, the reward was well worth the pain. In Denny’s case, his team gained a better understanding of RNA folding. Such is life, do it in yourself.

Biophysics on a chip

When GAIIx dropped in 2008, it was a hot commodity. Some sequencing centers had dozens of devices, costing around US$600,000; In 1 week, a machine can pull out the 30 billion letter bases that make up DNA. But by 2011, when Greenleaf set up its lab at Stanford, the industry rapidly shifted to hardware—such as the Illumina HiSeq 2000—that was more efficient and user-friendly, and people were giving their old machines away. “They’re basically big paperweights,” Greenleaf says.

Illumina sequencers automate a sequencing-by-synthesis process. A DNA library is randomly arranged on a device called a flow cell, and stretched in place to form small groups of approximately 1,000 molecules, each representing a single piece of genetic information.

The building blocks of DNA, or nucleotides, are then transferred onto a chip, each with a unique fluorescent signature and a reversible chemical modification.

This process ensures that only one nucleotide can be added to each cluster. The sequencer then images the array, and ‘calls’, or reads, based on the color at each position, which base was added. Then the modification is removed, and the process is repeated, allowing the entire sequence to be identified by base.

At their core, these devices are high-end microscopes with liquid handlers that help move reagents around. Some of their components – notably cameras, lasers and moving stages – can cost thousands of dollars. In 2009, Christopher Burge, an RNA biologist at the Massachusetts Institute of Technology in Cambridge, realized that it might be possible to rearrange that hardware to do something else.

Basics of hacking

“GAII is basically a pumping system that pumps things onto a flow cell and then to a fancy imaging system,” Burge says. “We realized that, well, maybe you can pump other things onto the flow cell.”

This, he says, is because GAIIx was an ‘open system’, controlled using editable configuration files called recipes and loaded with reagents that could be replaced by simply substituting one tube for another.

Could have done. From the inside, the machine was evenly spaced, with off-the-shelf, third-party components held together with cable ties. “In retrospect, this looks like a high-school science project,” says Gary Schroth, a biochemist who directs the genomics-applications group at Illumina in San Diego, Calif., and who in his early studies Collaborated with Burge.

The new Illumina equipment, by contrast, is more polished with custom hardware, hardwired control software and barcoded reagents – features that improve the user experience but deter hacking.

Jacob Tome John Liss, a molecular biologist at Cornell University in Ithaca, New York.

The pros and cons of mentoring by Skype

The pros and cons of mentoring by Skype

Shoba is a Research Fellow at the Amarnath Institute of Cellular Medicine, Newcastle University, UK, and mentored by Judy Allen, an immunobiologist at the University of Manchester, UK. Their mentorship arrangement was conducted as part of the UK Academy of Medical Sciences Springboard programme, which provides financial and practical support to biomedical researchers.

The research focus of Amarnath’s lab is understanding how the immune system inhibits the responses of particular proteins (known as immunosuppressants) in the body, specifically cell-surface receptors such as PD-1, T cells and innate lymphoid cells. how to control. Allen’s laboratory worm parasites study the interactions between worms and their hosts.

Shoba Amarnath

I applied for the Springboard program because it came with a bespoke mentoring system. I liked the fact that this is not hierarchical advice. This is not a Senior Principal Investigator (PI) in your department. Instead, it is a person who is expert in his field. And you have to choose them instead of being assigned to them. I chose someone in immunology. I wanted to understand the scenario.

Judy gives me a broader perspective. Although I did my PhD in the United Kingdom, I never really got into the scientific culture here. After moving here from Chennai, India, I completed my Master’s and PhD in Cancer Immunotherapy at Hull University, UK.

I then did a postdoc in Wanjun Chen’s lab at the US National Institutes of Health (NIH) in Bethesda, Maryland. After spending a total of ten years at the NIH, you forget how everything else works. For example, the NIH receives major funding from the federal government, and researchers there do not write grant applications at all. That’s why I never wrote one. I did not know.

I first spoke to Judy in late 2016 and we met for the first time in December of that year. We communicate using Skype, but also in immunology meetings. I e-mail him about my progress and I’ve contacted him again to discuss some of the things happening in my group, including a paper I’m working on for the Journal of Experimental Medicine. was.

She really centers my thought processes. A few months ago, for example, she suggested that the next step for me would be to focus on a larger grant. As a new Pi, this is all very helpful. You don’t know what the important milestones are. In academia this is all ambiguous. There are no set rules.

I give advice to people now and I ask Judy about it. It’s important for junior colleagues to be there. As PI, it is my thoughts that are being taken forward. I really try to step aside and let the students drive the projects and their careers.

One thing I am learning, which is very difficult, is not to push people to academic training. Academics should not always be the focus. It is a bit difficult for an academic to reconcile. I was fortunate enough to be aware of elective tracks, as all my friends at NIH went on to non-academic careers, including policy and grant management. We need scientists in these careers who can advocate for science.

Judy allen

When the people of Academy of Medical Sciences asked me to mentor Shoba, they said that I have to do a mentoring course. One thing I learned from that course that I didn’t fully appreciate is advising someone in your lab who you have a vested interest in, and someone who is outside of your direct influence.

The people I mentor through the academy are completely far from anything with me. I’m more likely to tell a remote person that they should quit or something isn’t working, but I would find it very hard to tell someone in Manchester, as I know them personally and their success . There’s a reflection on me in my lab. I need them to be successful. This is a very different process.

I mentor two people through the Springboard program. I’m well aware of the internal politics of where Shoba and the other person works, so a lot of advice in distance mentoring focuses on how well someone treats their head of department. does.

I try to establish whether they have a good relationship or not and urge them to go to him first. Sometimes women don’t think to ask: “What do you expect from me? What will it take for me to reach the next promotion stage?” I emphasize that whatever I say should not be the last word.

Skype is a wonderful invention and I’m happy to use it at any time, but I think it’s important to meet in person. I have a meeting in Newcastle in a few weeks and would suggest to Shoba that we meet again for lunch.

The main challenge of remote mentoring is that you don’t click with anyone.

Major European Railways sign MoU for identification

Major European Railways sign MoU for identification

At the Third Additive Manufacturing Forum in Berlin, German railway company Deutsche Bahn (DB), Austrian Federal Railways (OBB), Italian train operator Trenitalia and state-owned Swedish railway company SJ signed a Memorandum of Understanding (MoU) by proxy of seven. European Railways.

The MoU signed on 15 March 2019 indicates a pledge by the railway companies to cooperate in the working group RAILiability under the Mobility Go Additive Network.

The Relability Working Group was formed with the objective of identifying clear technology use cases for additive manufacturing.

Mobility becomes additive – what is it?

Four railway institutions are each a member of the Mobility Go Additive Network. This network of companies from the mobility and logistics business has come together to advance the application of additive manufacturing, with a particular focus on the production of spare parts for the transportation sector.

The Mobility Go Additive Network will act as a central platform to promote “mutual development of the competencies of its members”. Thus, along with having railway institutions within their network, major additive manufacturing enterprises such as EOS and Stratasys are also part of Mobility Go Additive to work with companies seeking to implement additive manufacturing.

DB, BB, Trenitalia and SJ, and three other European railways form the Reliability Working Group of Mobility Go Additive, which focuses exclusively on rail networks and rolling stock. The group aims to “identify technical applications that show the AM market concrete areas of action and potential.”

Deutsche Bahn and 3D Printing

The Mobility Go additive platform has previously linked Deutsche Bahn with Berlin-based 3D printing software developer 3YOURMIND, which is also a member of the network. DB has used 3YOURMINDS’ technology to reduce the cost of maintaining inventory by using 3D printing to produce on demand replacement.

The companies collaborated to build a ‘digital spare parts warehouse’ using 3YOURMIND’s Additive Manufacturing Part Identifier (AMPI). DB employees are encouraged to submit their 3D printing ideas and suggestions for spare parts that DB can develop using the AMPI software.

The development of a digital spare parts warehouse builds on DB’s previous initiative to 3D print its spare parts. Since then, DB has been able to 3D print approximately 15,000 spare parts and other products, helping to achieve significant savings and reducing vehicle downtime.

Thanks to Energica CRP Group for the Moto World Cup

Thanks to Energica CRP Group for the Moto World Cup

Italian electric motorbike maker Energica is back to participate in the opening ceremony of the 2019 FIM Enel MotoE World Cup which begins in July this year.

In March, the MotoE World Cup suffered a setback when all eighteen bikes participating in the event, including the Ego Corsa of Energica, were destroyed by fire in the city of Jerez, Spain, where the bikes were housed. Thanks to help from CRP Group’s subsidiaries, 3D printing materials manufacturer CRP Technology and construction services provider CRP Meccanica, Energica is now ready to participate in the Cup.

CRP Meccanica and CRP Technology CEO Franco Sevolini commented, “The next day after the fire broke out in Jerez, it was clearly known that a special effort was to be made: Now, as Energica’s technical partners, I am very proud of I can say we did it!”

Crp technology windform material

Headquartered in Modena, Energica is a subsidiary of the CRP Group, which includes CRP Technology, CRP Meccanica and CRP USA. Energica manufactures 100% electric motorbikes that are partially 3D printed using Windform, a material owned by CRP Technology.

Used in automotive, aerospace and medical applications, windform can be 3D printed and CNC machined. Since its first release, CRP has added to the range of windform materials which now includes the P-Line range for high speed sintering.

In addition to R&D and materials manufacturing, CRP Technology and CRP Meccanica also provide machining services such as CNC machining and 3D printing. In its rapid prototyping department, CRP Technology uses 3D systems and twenty-five industrial 3D printers from Ricoh, among other manufacturers.

Recover from fire

So far the bike manufacturer Energica has released four models: Eva, Ego, EsseEsse9, and Ego Corsa.

Energica is participating in the upcoming FIM Enel MotoE World Cup with Ego Corsa Motorbikes. After the fire, the partners were challenged with rebuilding the bike in just two months. Having succeeded in this feat, Cevolini called it “a true miracle”.

“Since the early hours after the unfortunate incident,” Sevolini said, “CRP Mechanica and CRP Technology have supported him in meeting his challenge with Energica.”

Study uses plankton genomes as global biosensors of ocean

Study uses plankton genomes as global biosensors of ocean

By analyzing the benefits and losses in the genes of the Fight Compliant Sampling in all major ocean areas of California, Irwin has so far made the most developed and high-resolution map to show that these lighting organisms either grow Forced or forced to customize the key nutrients, nitrogen, phosphorus and limited amounts of iron.

As part of the new Bio-Go-Ship Initiative, the UCI scientists spent eight deployment on six different research ships, 228 days in the ocean in the Atlantic, Pacific and Indian Oceans. They generated approximately 1,000 ocean metzenom from 930 places around the world, in which there was an average distance between 26.5 kilometers (about 16.5 miles) between collection points.

In a study published in science today, UCI researchers explained how they used a property of embedded information in microbial genes – especially in the form of bioscience of Sea Health and Productivity from Fight Complaced Proclococcus. The marine working in this area is interested in understanding that these organisms are struggling to find or use the essential substances necessary to grow and re-generate.

“Fitoplaccuts are based on the seafood web, and they are responsible for half a part of global carbon dioxide determination ongoing basis, so the health and distribution of these organisms is very important,” Senior co-author Adam Martini said, “Earth UCI Professor of System Science. “Knowledge obtained on these visits will help climate science predictions about the role of Fight Community in regulating carbon stock in the atmosphere and ocean.”

Since Microbial Fightplinkton live in large population and rapidly life cycle, researchers suggest that changes in community structure and genomic material can provide initial warnings about environmental changes and analyzed the ocean physics and chemistry so far Can perform rapidly.

UCI graduate student leader writer Lucas Uychar said in ecological science and evolutionary biology, “Nitrogen, phosphorus and iron limit in many surface ocean areas are almost impossible; The amount of these elements is very low.” . “But measuring the changes in the Proclococus genes involved in the upliftment of major nutrients, and its combination provides a strong indicator of geography of nutrient stress.”

The authors reported that all the Proclococus Jinom includes a certain gene, which allows Phytoplakton to assimilate directly to inorganic phosphate in seawater. But when this compound occurs in low supply, Fight is adapted by receiving a gene, which enables cells to take decomposed organic phosphorus, which can be found in their genome.

Researchers also studied many other instances of genetic adaptation for different levels of phosphorus, iron and nitrogen in the environment so that to see what Fight Commodity is constantly closed. What is the global map of the resulting nutrients. The researcher was also able to identify those areas where Phytoplankton experiences co-stress to include two or more elements, one of them is always nitrogen.

The team’s work expressed the northern Atlantic Ocean, the Mediterranean Sea and the Red Sea to be elevated phosphorus stress. Customized genotype for nitrogen stress is widely widespread in the so-called Olygotrophic areas where nutrients are low and oxygen is high, and the result of research samples suggests widespread adaptation for iron stress.

Analysis of phytoplankton genotype confirmed the known biographical patterns of approximate nutrient stress by various techniques, but it also disclosed the first unknown areas of the nutrient stress and co-stress.

Researchers understood the lack of nutrient stress in the Indian Ocean before their metadessonomic analysis, but their work helped to fill many vacant places. Now they know the Arab Sea Appelling area to become a field of iron stress, and they detected phosphorus stress associated with south-flowing ocean streams among many other findings.

Still, they say, always more to learn.

“Our work highlights the difference in our measurement of high latitude environments, in most Pacific Ocean, and in deep water ecological system,” said UCI posttocal scholar in Earth System Science. “We have progressed on our recent campaigns, it inspires us to extract and cover the whole planet.”

Researchers find link between earthquake timing and water cycle in Taiwan

Researchers find link between earthquake timing and water cycle in Taiwan

Taiwan, Canada and U.S. A team of researchers got a link between the water cycle and earthquake time in Taiwan. In his paper published in the progress of science, the group describes its study of the water cycle in Taiwan and why it appears to be related to the time of earthquake.

This work started when one of the team members saw that big earthquakes in Taiwan were often in dry weather. Taiwan is under heavy rain and continuous tyzoon every year between May and September.

In other months, the amount of rain is very low. Pre-research has shown that due to dramatic changes in the amount of rain, the level of ground water changes dramatically.

In this new effort, the researchers thought that the level of ground water is reduced, which leaves empty cavity under the ground, may be behind some of the many earthquakes experienced by the country.

To find out, he collected both earthquake and rain data for the country, in some cases going back up for several hundred years. They allow satellite data which allowed to measure water storage on the island.

Researchers found that swelling activity was before the beginning of monsoon season during the dry season, especially during February, March and April during the dry season. He also found that seismic activity was the most calm from July to September-was usually the biggest part of the year.

Researchers also found that due to the fall below the bottom of low water during the dry season, gradually increased the obstacles of the earthquake as a result of the land.

He also found that there were various factors involved in earthquakes on east of West versus island. There was another complex pattern in the earthquake on the east side of the island, and less related to the weather.

Researchers noticed that the annual stress can contribute deep stress for the land under the island which are sometimes resulted in the breakdown of large defects, which are some big earthquakes which sometimes do rocks. Their conclusions can affect other parts of the world, which experiences dramatic fluctuations in the rain every year.

Deciduous trees offset carbon loss from Alaskan boreal fires

Deciduous trees offset carbon loss from Alaskan boreal fires

Alaska Borel Forest is releasing more serious and continuous fire carbon and nitrogen in the atmosphere from the trees and soil burned, a trend that accelerate climate warming. But the new research published this week in Journal Science shows that the deciduous trees change the spousing forests for that loss, and collect four times faster at 100 years of fire intervals.

Studying under the leadership of a team of researchers at the center of ecological mechanism science and society at the University of Northern Arizona shows that these rapidly growing, less flammable deciduous forest fire patterns and a stable against the loss of nutrients’ Firebrake can work as’ area.

The study began due to the dramatic 2004 fire season in Alaska when an area was burnt seven times long. Historically, more than half of this wild terrain has been dominated by a black spouse, but after the fire, the rapidly growing aspen and the bite are changing some of these stands.

75 Black Spots made from the researchers of the team, Northern Arizona University, Alaska University, Aubner University, and Saskachwan University burned in 2004 and followed their recovery in the next 13 years.

He also collected a series of data from the clay and soil and soil of various ages and burned severity to make a cronusquence, a kind of scientific time-defaults which allow researchers to move rapidly through 100 years fire cycle. So that to see how to retrieve the forest and how to change.

Michel Mac, chief writer of biology and study at the University of Northern Arizona, said, “In 2005, I thought there was no way to recover carbon who lose these forests in this fire.” “The literature is full of papers, more serious fire can be replaced before the next fire. But not only did we see these deciduous trees for those losses, they did so fast.”

The team found that the new aspen and the bear tree where Black Sprus burned carbon and nitrogen collected compared to the ground, contrary to soil organic layer, stored it in its wood and leaves.

And at the end of an estimated 100 year cycle, more nitrogen was recovered in the form of fire in the deciduous stand, and more carbon was lost, resulting in net ecological mechanisms increased in carbon balance. Calculation of this balance is important because the scientists work to understand ways to change such northern forests, and the effect of those changes on global carbon images.

Forest Ecology and a Assistant Professor Hertar Alexander in Auburn said, “I was surprised that the deciduous trees can fill the lost carbon so effectively and efficiently.”

“Even though a lot of carbon is combustion and emitted in that environment when the black spouse burns severely, deciduous trees which often replace them, to retrieve and store carbon in their above leaves and wood There is a wonderful ability. ”

“In one area with only five common tree species, this study shows how the change in the structure of the tree can dramatically change the pattern of carbon storage in Borel forests,” said the Northern researcher of Alaska-Fairbanks University Jill Johnstone and Study.

McKek said, “Carbon is just a piece of puzzle, who said that there are other important responses on the climate in the deciduous forests, or the endway effects.”

We know that these forest help in calm regional climate, and we know That they are less ignited, so the possibility of spreading fire is less. Together Together, these effects make a relatively strong set of stabilizing climate reactions in the borel forest. ”

But there is a lot that researchers do not know about the fate of deciduous Borel forests in a hot world.

“Mature deciduous trees die, will they be replaced with trees with the same structure, structure, and carbon storage capabilities?” Alexander asked. “And will they be cured with fire with the same carbon storage capabilities?”

“Changes in rapidly growing deciduously increasing rapidly increasing rapidly in the forest of Borel can balance the effects of acute fire rule in Borel’s forest,” said Islike Myers-Smith, a global change at the University of Edinburgh which was not included in it. Study. “But it is seen that how carbon balances the balance in future with sharp warming on high latitudes.”

Mac said that continuous climate warming can undo carbon-creeting benefits, which represent these trees. “Carbon should reside long on the scenario because the deciduous forests are less flammable.

But the flammability is not stable. The climate will pass a threshold where things will be so hot and dry, even the deciduous forest will burn. Ask How strong will the weak effect of low flammability, and how long will it run? ”

PermaFrost carbon also makes the picture complex.