The Future of Synthetic Biology: Reading and Writing DNA Using Nanopores

Biology is nothing more than a computational system. Granted, it’s far more sophisticated than any other computer available to us today, but we’re slowly beginning to learn how to read and write DNA as we would with code. Thanks to a group of researcher fellows of the Institute of Electrical and Electronics Engineers (IEEE), we’ve now taken one extra step towards a future of synthetic biology.

Published on IEEE Access, researchers used nanopores – a tiny hole inside of a membrane that allows singular molecules of DNA to pass through – in order to read DNA and proteins, and subsequently write new DNA by inserting mini-genes into mammalian cells.

“In conclusion, the future is brilliant, if you think small and do a bit more research. Nanopores can be used to both READ: detect and sequence DNA and sense proteins, and WRITE DNA into cells. These tools will provide methods to explore areas of biology either impractical to reach, or at least logistically intractable.” – IEEE Study

Photo Credit: IEEE / Genetic Literacy Project

Not only is this breakthrough research helping us better understand our own biology, but is equally bringing everyone else along for the ride. By simplifying the methodological ability to sequence single-cell DNA using nanopores, these researchers have provided molecular and sub-molecular analysis within reach for all bench-top scientists and clinical labs outside of the confines of genomics or spectrometry specialists.

But don’t jump off your seats just yet in celebration, because more research is needed for synthetic biology to make a significant impact.

“Prospects for synthetic biology (and manufacturing) using nanopores to program cells (or micelles) and deliver materials are especially alluring. Chemical processing generally becomes more efficient in a microreactor because mass transport limitations are practically eliminated. However, the synthesis, so far, has been focused at a single cell or few nano-reactor level; it needs to be scaled up.” – IEEE Study

FUTURE IMPLICATIONS

The precision of molecular configuration of ions passing through the pores of membranes points to a future of tiny research making extremely large impacts on the health of society. The future of medicine will largely rely on our ability to read and write DNA like code in order to upgrade our bio-computational systems against fatal diseases. By using nanopores as a means of reading and writing DNA, we are steadily revealing the secrets of our own biology, consequently unlocking future possibilities of enhancing our longevity.

ORIGINAL: Serious Wonder
BY B.J. MURPHY

Hand-Held Spectroscopy Tool Lets You Examine the Molecular Composition of Your Food

Up on Mars, the Curiosity Rover uses its spectrometers to examine the chemical composition of the rocks and dirt on the red planet. Now the Israeli startup Consumer Physics has developed a tool that lets you conduct similar experiments in your own backyard or at your dinner table.

The company launched a Kickstarter campaign today with the goal of raising US $200 000 to fund the first production run of its hand-held spectrometer, which is about the size of a flash drive.

Using near-infrared spectroscopy, the device, called SCiO, shines light on a sample and measures the light absorption patterns of the molecules therein. It then identifies the object by its optical signature, and gives the user information about the object's molecular composition. It uses bluetooth to link to the user's smartphone, where an app manages the data.

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In a product demo for IEEE Spectrum last week, company CEO Dror Shalon held up a prototype SCiO to a block of Gouda he had just bought at Walgreens. After a brief flash of light and a few seconds of analysis, Shalon's smartphone reported that the item was: cheese. While that might not seem like the most useful announcement for a functional human being with eyes, the SCiO can provide more info. After following a prompt to enter the portion size (which was on the cheese's packaging), the app displayed that cheese's calories per serving, as well as fats, carbohydrates, and proteins. Of course, all that info was also on the cheese's packaging. But Shalon says the SCiO's abilities will shine forth at restaurants and anywhere people are grabbing food on the go. 

Shalon thinks that consumer spectroscopy is an idea who's time has come. Today's quantified self gadgets let us track our bodies with unprecedented recision—we can count our steps taken, calories burned, and much more. But people who want that kind of information about the materials around them have been out of luck so far. "When we came up with this vision, I went to Amazon to search, because I was sure that it must exist already," says Shalon. When his search came up empty, he and his team started working.

Kickstarter backers who donate $149 will get the SCiO in December, along with free downloads of all the SCiO-specific apps that Consumer Physics will develop over the next two years. The company has already developed apps for identifying and authenticating pharmaceuticals, for checking the hydration of plants, and for measuring the sugar content of fruit. Shalon is hoping that third-party developers will find many other things to do with SCiO. "That's the major reason we’re doing the Kickstarter campaign, to get the device into the hands of the early adopters," he says.

ORIGINAL: IEEE Spectrum

By Eliza Strickland
30 Apr 2014 | 13:00 GMT

The #1 Career Mistake Capable People Make

ORIGINAL: LinkedIn

Greg McKeown

December 06, 2012

I recently reviewed a resume for a colleague who was trying to define a clearer career strategy. She has terrific experience. And yet, as I looked through it I could see the problem she was concerned about: she had done so many good things in so many different fields it was hard to know what was distinctive about her.

As we talked it became clear the resume was only the symptom of a deeper issue. In an attempt to be useful and adaptable she has said yes to too many good projects and opportunities. She has ended up feeling overworked and underutilized. It is easy to see how people end up in her situation:

Step 1: Capable people are driven to achieve.

Step 2: Other people see they are capable and give them assignments.

Step 3: Capable people gain a reputation as "go to" people. They become "good old [insert name] who is always there when you need him." There is lots right with this, unless or until...

Step 4: Capable people end up doing lots of projects well but are distracted from what would otherwise be their highest point of contribution which I define as the intersection of talent, passion and market (see more on this in the Harvard Business Review article The Disciplined Pursuit of Less). Then, both the company and the employee lose out.

When this happens, some of the responsibility lies with out-of-touch managers who are too busy or distracted to notice the very best use of their people. But some of the responsibility lies with us. Perhaps we need to be more deliberate and discerning in navigating our own careers.

In the conversation above, we spent some time to identify my colleague's Highest Point of Contribution and develop a plan of action for a more focused career strategy.

We followed a simple process similar to one I write about here: If You Don’t Design Your Career, Someone Else Will. My friend is not alone. Indeed, in coaching and teaching managers and executives around the world it strikes me that failure to be conscientious about this represents the #1 mistake, in frequency, I see capable people make in their careers.

Using a camping metaphor, capable people often add additional poles of the same height to their career tent. We end up with 10, 20 or 30 poles of the same height, somehow hoping the tent will go higher. I don't just mean higher on the career ladder either. I mean higher in terms of our ability to contribute.

The slightly painful truth is, at any one time there is only one piece of real estate we can "own" in another person’s mind. People can't think of us as a project manager, professor, attorney, insurance agent, editor and entrepreneur all at exactly the same time. They may all be true about us but people can only think of us as one thing first. At any one time there is only one phrase that can follow our name. Might we be better served by asking, at least occasionally, whether the various projects we have add up to a longer pole?

I saw this illustrated some time ago in one of the more distinctive resumes I have seen. It belonged to a Stanford Law School Professor [there it is: the single phrase that follows his name, the longest pole in his career tent]. His resume was clean and concise. For each entry there was one impressive title/role/school and a succinct description of what he had achieved. Each sentence seemed to say more than ten typical bullet points in many resumes I have seen. When he was at university he had been the student body president, under "teaching" he was teacher of the year and so on.

Being able to do many things is important in many jobs today. Broad understanding also is a must. But developing greater discernment about what is distinctive about us can be a great advantage. Instead of simply doing more things we need to find, at every phase in our careers, our highest point of contribution.

One cell is all you need

ORIGINAL: News Harvard

By Peter Reuell. Harvard Staff Writer

January 4, 2013

Innovative technique can sequence entire genome from single cell

Rose Lincoln/Harvard Staff Photographer. Mallinckrodt Professor of Chemistry and Chemical Biology Xiaoliang Sunney Xie (from left) has co-authored a paper on gene sequencing with graduate student Alec Chapman and postdoctoral fellow Chenghang Zong. The paper demonstrates a new method for DNA amplification that could signal a breakthrough in genomics.

The notion that police can identify a suspect based on the tiniest drop of blood or trace of tissue has long been a staple of TV dramas, but scientists at Harvard have taken the idea a step further. Using just a single human cell, they can reproduce an individual’s entire genome.

As described in a Dec. 21 paper in Science, a team of researchers, led byXiaoliang Sunney Xie, the Mallinckrodt Professor of Chemistry and Chemical Biology, and made up of postdoctoral fellow Chenghang Zong, graduate student Alec Chapman, and former graduate student Sijia Lu, developed a method — dubbed MALBAC, short for Multiple Annealing and Looping-based Amplification Cycles — that requires just one cell to reproduce an entire DNA molecule.

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More than three years in the making, the breakthrough technique offers the potential for early cancer treatment by allowing doctors to obtain a genetic “fingerprint” of a person’s cancer from circulating tumor cells. It also could lead to safer prenatal testing for a host of genetic diseases.

“If you give us a single human cell, we report to you 93 percent of the genome that contains three billion base pairs, and if there is a single base mutation, we can identify it with 70 percent detectability, with no false positives detected,” Xie said. “This is a major development.”

In a second paper, published simultaneously, researchers from Xie’s lab worked with scientists at Peking University in China to demonstrate MALBAC by sequencing 99 sperm cells from one individual and examining the paternal and maternal contribution to each cell’s genome.

As its name suggests, Xie said, MALBAC is a type of DNA amplification that allows researchers to duplicate the single DNA molecule present in a cell many times so it can be analyzed in the lab.

“While other methods of DNA amplification exist, most — like polymerase chain reaction (PCR) or multiple displacement amplification (MDA) — suffer from a specific problem,” Xie said. “Because they amplify exponentially, both have bias. They dramatically amplify some parts of the genome, but amplify others very little.”

By comparison, he said, MALBAC relies on linear amplification, meaning it is able to minimize the sequence-dependent bias.

Just as it does with other methods, the amplification process begins by splitting the DNA double helix into two single strands. Xie’s team then adds a random “primer” — tiny fragments of DNA — that binds in dozens of locations along each strand.

To extend those primers, Xie’s team used a DNA polymerase, the same cellular “machine” that synthesizes DNA as cells divide. Using that machine, researchers are able to extend the primers from as few as seven bases to as many as 2,000. Upon heating, they break the elongated primers apart from the original DNA, yielding half products.

When those half products are then amplified using the same primers, the two ends of the DNA combine, forming a loop that prevents it from being amplified again. The leftover half products and the original DNA are subject to another cycle of amplification. After five cycles of such linear pre-amplification, the full product is amplified by PCR to produce enough material for sequencing.

Despite the high coverage, DNA polymerases do occasionally make errors, Xie explained. To ensure that the genome produced by MALBAC is accurate, researchers turned to a different technique.

“Many diseases are associated with a single base mutation,” Xie said. “The challenge, however, is that finding one mutation in more than 3 billion base pairs is like looking for a needle in a haystack. Earlier techniques, like PCR or MDA, start with many cells, making the challenge even greater; a single mutation simply gets lost in the process. MALBAC, however, starts with a single cell, so it is easier to identify those mutations when they happen.”

To ensure MALBAC’s accuracy, Xie’s team simply let the original cell divide.

While the polymerase that researchers use to build the DNA sequence is highly accurate, only making one mistake per 10,000 bases, letting the cell divide gives researchers a chance to double check its work.

“The chances of the same mistake being made at the same base position are about one in 100 million,” Xie said. “If we let the cells divide again, and sequence three cells, the chances go up to one in 10 billion, less than the number of bases in the entire DNA molecule, so we can remove all the false positives.

“Getting that level of accuracy is very important, because if a doctor tells a patient that he detects a mutation, he doesn’t want to be wrong,” he continued. “When we use MALBAC, if a mutation appears in two or three related cells, we know it must be a real mutation.”

As a demonstration of MALBAC’s power, Xie and his team monitored the mutations that arose in a single cancer cell as it divided over 20 generations, and uncovered as many as 50 newly acquired mutations.

“This is the first time the mutation rate of a human cell has been measured directly,” Xie said. “Because we can now see the unique, newly acquired bases, we can study the dynamics of the genome in a way that was not possible before.”