Tag Archives: DNA

Science cakery

I have to thank Dean Burnett for his science cake extravagance on the Guardian science blogs. Here’s a few pictures of cake to tantalize you from Burnett’s Aug. 12, 2015 posting,

An evolution-of-life cake from @OxUniEarthSci Palaeontology Group. Bizarre how this life-sciences cake seems to defy physics with its structure. Photograph: @JackJMatthews

An evolution-of-life cake from @OxUniEarthSci Palaeontology Group. Bizarre how this life-sciences cake seems to defy physics with its structure.
Photograph: @JackJMatthews

A cake shaped like a subject entering an MRI scanner for @ImanovaImaging’s 1st birthday party. Because why not? Photograph: @M_Wall

A cake shaped like a subject entering an MRI scanner for @ImanovaImaging’s 1st birthday party. Because why not?
Photograph: @M_Wall

Katie Watkins created TMS coils on talking brains. For the record, it is not necessary or even helpful for the brain to be exposed during TMS. Photograph: Kate Watkins

Katie Watkins created TMS coils on talking brains. For the record, it is not necessary or even helpful for the brain to be exposed during TMS. Photograph: Kate Watkins

Katie Grifiths, posing with a DNA cake made by her sister Emma. What’s with these biology-themed cakes and their ability to overrule gravity? Do NASA know about this? Photograph: Katie Griffiths

Katie Grifiths, posing with a DNA cake made by her sister Emma. What’s with these biology-themed cakes and their ability to overrule gravity? Do NASA know about this?
Photograph: Katie Griffiths

Marilyn Audlsey produced this particles-in-a-cloud-chamber ginger cake. I’m not even going to pretend to know what that is, but it makes for a nice looking cake. Photograph: Marilyn Audsley

Marilyn Audlsey produced this particles-in-a-cloud-chamber ginger cake. I’m not even going to pretend to know what that is, but it makes for a nice looking cake. Photograph: Marilyn Audsley

And this is the last one I’m including,

Sara Barnes did this @ATLASexperiment. At last, the money spent on the Lare Hadron Collider starts to show useful results. Photograph: Sarah Barnes

Sara Barnes did this @ATLASexperiment. At last, the money spent on the Lare Hadron Collider starts to show useful results.
Photograph: Sarah Barnes

Burnett has many more areas of science memorialized in cake in his Aug. 12, 2015 posting.

I last featured science and cakes in a March 31, 2012 posting about the periodic table of elements and cupcakes. On a closely related note, I wrote about mathematics and baking in a June 28, 2013 posting.

DNA (deoxyribonucleic acid) scaffolding for nonbiological construction

DNA (deoxyribonucleic acid) is being exploited in ways that would have seemed unimaginable to me when I was in high school. Earlier today (June 3, 2015), I ran a piece about DNA and data storage as imagined in an art/science project (DNA (deoxyribonucleic acid), music, and data storage) and now I have this work from the US Department of Energy’s (DOE) Brookhaven National Laboratory, from a June 1, 2015 news item on Nanowerk,

You’re probably familiar with the role of DNA as the blueprint for making every protein on the planet and passing genetic information from one generation to the next. But researchers at Brookhaven Lab’s Center for Functional Nanomaterials have shown that the twisted ladder molecule made of complementary matching strands can also perform a number of decidedly non-biological construction jobs: serving as a scaffold and programmable “glue” for linking up nanoparticles. This work has resulted in a variety of nanoparticle assemblies, including composite structures with switchable phases whose optical, magnetic, or other properties might be put to use in dynamic energy-harvesting or responsive optical materials. Three recent studies showcase different strategies for using synthetic strands of this versatile building material to link and arrange different types of nanoparticles in predictable ways.

The researchers have provided an image of the DNA building blocks,

Controlling the self-assembly of nanoparticles into superlattices is an important approach to build functional materials. The Brookhaven team used nanosized building blocks—cubes or octahedrons—decorated with DNA tethers to coordinate the assembly of spherical nanoparticles coated with complementary DNA strands.

Controlling the self-assembly of nanoparticles into superlattices is an important approach to build functional materials. The Brookhaven team used nanosized building blocks—cubes or octahedrons—decorated with DNA tethers to coordinate the assembly of spherical nanoparticles coated with complementary DNA strands.

A June 1, 2015 article (which originated the news item) in DOE Pulse Number 440 goes on to highlight three recent DNA papers published by researchers at Brookhaven National Laboratory,

The first [leads to a news release], published in Nature Communications, describes how scientists used the shape of nanoscale building blocks decorated with single strands of DNA to orchestrate the arrangement of spheres decorated with complementary strands (where bases on the two strands pair up according to the rules of DNA binding, A to T, G to C). For example, nano-cubes coated with DNA tethers on all six sides formed regular arrays of cubes surrounded by six nano-spheres. The attractive force of the DNA “glue” keeps these two dissimilar objects from self-separating to give scientists a reliable way to assemble composite materials in which the synergistic properties of different types of nanoparticles might be put to use.

In another study [leads to a news release], published in Nature Nanotechnology, the team used ropelike configurations of the DNA double helix to form a rigid geometrical framework, and added dangling pieces of single-stranded DNA to glue nanoparticles in place on the vertices of the scaffold. Controlling the code of the dangling strands and adding complementary strands to the nanoparticles gives scientists precision control over particle placement. These arrays of nanoparticles with predictable geometric configurations are somewhat analogous to molecules made of atoms, and can even be linked end-to-end to form polymer-like chains, or arrayed as flat sheets. Using this approach, the scientists can potentially orchestrate the arrangements of different types of nanoparticles to design materials that regulate energy flow, rotate light, or deliver biomolecules.

“We may be able to design materials that mimic nature’s machinery to harvest solar energy, or manipulate light for telecommunications applications, or design novel catalysts for speeding up a variety of chemical reactions,” said Oleg Gang, the Brookhaven physicist who leads this work on DNA-mediated nano-assembly.

Perhaps most exciting is a study [leads to a news release] published in Nature Materials in which the scientists added “reprogramming” strands of DNA after assembly to rearrange and change the phase of nanoparticle arrays. This is a change at the nanoscale that in some ways resembles an atomic phase change—like the shift in the atomic crystal lattice of carbon that transforms graphite into diamond—potentially producing a material with completely new properties from the same already assembled nanoparticle array. Inputting different types of attractive and repulsive reprogramming DNA strands, scientists could selectively trigger the transformation to the different resulting structures.

“The ability to dynamically switch the phase of an entire superlattice array will allow the creation of reprogrammable and switchable materials wherein multiple, different functions can be activated on demand,” Gang said.

Here are links to and citation for all three papers,

Superlattices assembled through shape-induced directional binding by Fang Lu, Kevin G. Yager, Yugang Zhang, Huolin Xin, & Oleg Gang. Nature Communications 6, Article number: 6912 doi:10.1038/ncomms7912 Published 23 April 2015

Prescribed nanoparticle cluster architectures and low-dimensional arrays built using octahedral DNA origami frames by Ye Tian, Tong Wang, Wenyan Liu, Huolin L. Xin, Huilin Li, Yonggang Ke, William M. Shih, & Oleg Gang. Nature Nanotechnology (2015) doi:10.1038/nnano.2015.105 Published online 25 May 2015

Selective transformations between nanoparticle superlattices via the reprogramming of DNA-mediated interactions by Yugang Zhang, Suchetan Pal, Babji Srinivasan, Thi Vo, Sanat Kumar & Oleg Gang. Nature Materials (2015) doi:10.1038/nmat4296 Published online 25 May 2015

The first study is open access, the second is behind a paywall but there is a free preview via ReadCube Acces, and the third is behind a paywall.

DNA (deoxyribonucleic acid), music, and data storage

David Bruggeman (Pasco Phronesis blog) has written up, as he so often does, a fascinating art/science piece in his May 28, 2015 post (Note: A link has been removed),

Opening next month [June 2015] at the Dilston Grove Gallery at GDP London is Music of the Spheres, an exhibition that uses bioinformatics to record music.  Dr. Nick Goldman of the European Bioinformatics Institute has been working on new technologies for encoding large amounts of information into DNA.  Collaborating with Charlotte Jarvis, the two have worked on installations of bubbles that would contain DNA encoded with music (the DNA is suspended in soap solution).

There’s more information about the exhibit on the Music of the Spheres webpage on the CGP London website,

Music of the Spheres utilises new bioinformatics technology developed by Dr. Nick Goldman to encode a new musical recording by the Kreutzer Quartet into DNA.

The DNA has been suspended in soap solution and will be used by visual artist Charlotte Jarvis to create performances and installations filled with bubbles. The recording will fill the air, pop on visitors skin and literally bathe the audience in music.

Dr. Nick Goldman and Charlotte Jarvis have been working together for the past year to create a series of moving visual and musical experiences that explore the scope and future ubiquity of DNA technologies.

The Kreutzer Quartet’s new composition for string quartet loosely follows the traditional form of a concerto, in comprising of three musical movements. The second movement only exists in the form of a recording encoded into DNA.

For the exhibition the DNA will be suspended in soap solution and used to create silent installations filled with bubbles. The bubbles will be accompanied by a video projection showing the musicians playing in the server room of the European Bioinformatics Institute, Cambridge.

In response to the growing challenge of storing vast quantities of biological data generated by biomedical research Dr. Nick Goldman and the European Bioinformatics Institute have developed a method to encode huge amounts of information in DNA itself. Every day the huge quantities and speed of data pouring into servers gets larger. When research groups sequence DNA the file sizes are too large to be kept on local computers. It is this problem that was the motivation for Nick Goldman to develop his new technology. Their goal is a system that will safely store the equivalent of one million CDs in a gram of DNA for 10,000 years. Nick’s work was has been featured in The New York Times, The Guardian and on BBC News amongst other media outlets.

The Kreutzer Quartet will play the full-length composition live during the preview on 12 June [2015] timed with the setting of the sun through the large westerly windows. [emphasis mine] During the passage of the second movement the stage will fall silent, the music will be released into the auditorium in the form of bubbles. The performance will be accompanied by film projection and a discussion about the project.

The exhibit runs from June 12 – July 5, 2015. Hours and location can be found on the CGP website.

The Music of the Spheres DNA/music project was first mentioned here in a May 5, 2014 post about the launch of the book ‘Synthetic Aesthetics: Investigating Synthetic Biology’s Designs on Nature’. The launch featured a number of performances and events, scroll down abut 80% of the way for the then description of Music of the Spheres.

Electrifying DNA (deoxyribonucleic acid)

All kinds of things have electrical charges including DNA (deoxyribonucleic acid) according to an April 15, 2015 news item on Azonano,

Electrical charges not only move through wires, they also travel along lengths of DNA, the molecule of life. The property is known as charge transport.

In a new study appearing in the journal Nature Chemistry, authors, Limin Xiang, Julio Palma, Christopher Bruot and others at Arizona State University’s Biodesign Institute, explore the ways in which electrical charges move along DNA bases affixed to a pair of electrodes.

Their work reveals a new mechanism of charge transport that differs from the two recognized patterns in which charge either tunnels or hops along bases of the DNA chain.

An April 13, 2015 Arizona State University (ASU) news release (also on EurekAlert and dated April 14, 2015), which originated the news item, explains why this ‘blue sky’ research may prove important in the future,

Researchers predict that foundational work of this kind will have important implications in the design of a new generation of functional DNA-based electronic devices as well as providing new insights into health risks associated with transport-related damage to DNA.

Oxidative damage is believed to play a role in the initiation and progression of cancer. It is also implicated in neurodegenerative disorders like Alzheimer’s, Huntington’s disease and Parkinson’s disease and a range of other human afflictions.

An electron’s movements plays an important role in your body’s chemical reactions (from the news release),

The transfer of electrons is often regarded as the simplest form of chemical reaction, but nevertheless plays a critical role in a broad range of life-sustaining processes, including respiration and photosynthesis.

Charge transport can also produce negative effects on living systems, particularly through the process of oxidative stress, which causes damage to DNA and has been invoked in a broad range of diseases.

“When DNA is exposed to UV light, there’s a chance one of the bases– such as guanine–gets oxidized, meaning that it loses an electron,” Tao says. (Guanine is easier to oxidize than the other three bases, cytosine, thymine, and adenine, making it the most important base for charge transport.)

In some cases, the DNA damage is repaired when an electron migrates from another portion of the DNA strand to replace the missing one. DNA repair is a ceaseless, ongoing process, though a gradual loss of repair efficiency over time is one factor in the aging process. Oxidation randomly damages both RNA and DNA, which can interfere with normal cellular metabolism.

Radiation damage is also an issue for semiconductor devices, Tao notes–a factor that must be accounted for when electronics are exposed to high-energy particles like X rays, as in applications designed for outer space.

Researchers like Xiang and Tao hope to better understand charge transport through DNA, and the molecule provides a unique testing ground for observation. The length of a DNA molecule and its sequence of 4 nucleotides A, T, C and G can be readily modified and studies have shown that both alterations have an effect on how electrical charge moves through the molecule.

When the loss of an electron or oxidation occurs in DNA bases, a hole is left in place of the electron. This hole carries a positive charge, which can move along the DNA length under the influence of an electrical or magnetic field, just as an electron would. The movement of these positively charged holes along a stretch of DNA is the focus of the current study.

The news release goes on to describe charge transport,

Two primary mechanisms of charge transport have been examined in detail in previous research. Over short distances, an electron displays the properties of a wave, permitting it to pass straight through a DNA molecule. This process is a quantum mechanical effect known as tunneling.

Charge transport in DNA (and other molecules) over longer distances involves the process of hopping. When a charge hops from point to point along the DNA segment, it behaves classically and loses its wavelike properties. The electrical resistance is seen to increases exponentially during tunneling behavior and linearly, during hopping.

By attaching electrodes to the two ends of a DNA molecule, the researchers were able to monitor the passage of charge through the molecule, observing something new: “What we found in this particular paper is that there is an intermediate behavior,” Tao says. “It’s not exactly hopping because the electron still displays some of the wave properties.”

Instead, the holes observed in certain sequences of DNA are delocalized, spread over several base pairs. The effect is neither a linear nor exponential increase in electrical resistance but a periodic oscillation. The phenomenon was shown to be highly sequence dependent, with stacked base pairs of guanine-cytosine causing the observed oscillation.

Control experiments where G bases alternated, rather than occurring in a sequential stack, showed a linear increase in resistance with molecular length, in agreement with conventional hopping behavior.

A further property of DNA is also of importance in considering charge transport. The molecule at room temperature is not like a wire in a conventional electronic device, but rather is a highly dynamic structure, that writhes and fluctuates.

The last bit about writhing and fluctuating makes this work sound fascinating and very challenging.

Here’s a link to and a citation for the paper,

Intermediate tunnelling–hopping regime in DNA charge transport by Limin Xiang, Julio L. Palma, Christopher Bruot, Vladimiro Mujica, Mark A. Ratner, & Nongjian Tao. Nature Chemistry 7, 221–226 (2015) doi:10.1038/nchem.2183 Published online 20 February 2015

This paper is behind a paywall.

Nature’s patterns reflected in gold nanoparticles

A 133 atom gold nanoparticle bears a resemblance to the Milky Way and to DNA’s (deoxyribonucleic acid) double helix according to an April 9, 2015 news item on ScienceDaily,

Our world is full of patterns, from the twist of a DNA molecule to the spiral of the Milky Way. New research from Carnegie Mellon chemists has revealed that tiny, synthetic gold nanoparticles exhibit some of nature’s most intricate patterns.

Unveiling the kaleidoscope of these patterns was a Herculean task, and it marks the first time that a nanoparticle of this size has been crystallized and its structure mapped out atom by atom. The researchers report their work in the March 20  [2015] issue of Science Advances.

“As you broadly think about different research areas or even our everyday lives, these kinds of patterns, these hierarchical patterns, are universal,” said Rongchao Jin, associate professor of chemistry. “Our universe is really beautiful and when you see this kind of information in something as small as a 133-atom nanoparticle and as big as the Milky Way, it’s really amazing.”

An April 8, 2015 Carnegie Mellon University news release (also on EurekAlert but dated April 9) by Jocelyn Duffy, which originated the news release, offers a description of gold nanoparticles along with details about the research,

Gold nanoparticles, which can vary in size from 1 to 100 nanometers, are a promising technology that has applications in a wide range of fields including catalysis, electronics, materials science and health care. But, in order to use gold nanoparticles in practical applications, scientists must first understand the tiny particles’ structure.

“Structure essentially determines the particle’s properties, so without knowing the structure, you wouldn’t be able to understand the properties and you wouldn’t be able to functionalize them for specific applications,” said Jin, an expert in creating atomically precise gold nanoparticles.

With this latest research, Jin and his colleagues, including graduate student Chenjie Zeng, have solved the structure of a nanoparticle, Au133, made up of 133 gold atoms and 52 surface-protecting molecules—the biggest nanoparticle structure ever resolved with X-ray crystallography. While microscopy can reveal the size, shape and the atomic lattice of nanoparticles, it can’t discern the surface structure. X-ray crystallography can, by mapping out the position of every atom on the nanoparticles’ surface and showing how they bond with the gold core. Knowing the surface structure is key to using the nanoparticles for practical applications, such as catalysis, and for uncovering fundamental science, such as the basis of the particle’s stability.

The crystal structure of the Au133 nanoparticle divulged many secrets.

“With X-ray crystallography, we were able to see very beautiful patterns, which was a very exciting discovery. These patterns only show up when the nanoparticle size becomes big enough,” Jin said.

During production, the Au133 particles self-assemble into three layers within each particle: the gold core, the surface molecules that protect it and the interface between the two. In the crystal structure, Zeng discovered that the gold core is in the shape of an icosahedron. At the interface between the core and the surface-protecting molecules is a layer of sulfur atoms that bind with the gold atoms. The sulfur-gold-sulfur combinations stack into ladder-like helical structures. Finally, attached to the sulfur molecules is an outer layer of surface-protecting molecules whose carbon tails self-assemble into fourfold swirls.

“The helical features remind us of a DNA double helix and the rotating arrangement of the carbon tails is reminiscent of the way our galaxy is arranged. It’s really amazing,” Jin said.

These particular patterns are responsible for the high stability of Au133 compared to other sizes of gold nanoparticles. The researchers also tested the optical and electronic properties of Au133 and found that these gold nanoparticles are not metallic. [emphasis mine] Normally, gold is one of the best conductors of electrical current, but the size of Au133 is so small that the particle hasn’t yet become metallic. Jin’s group is currently testing the nanoparticles for use as catalysts, substances that can increase the rate of a chemical reaction.

*ETA April 14, 2015 at 9015 PDT: Coincidentally, researchers in Finland have been examining gold nanoparticles and the size at which they are considered metals and at which they are considered molecules (mentioned in my April 14, 2015 posting [Gold atoms: sometimes they’re a metal and sometimes they’re a molecule]).*

Getting back to patterns, the researchers have provided an A-ray image of Au133,

 Caption: The X-ray crystallographic structure of the gold nanoparticle is shown. Gold atoms = magenta; sulfur atoms = yellow; carbon atoms = gray; hydrogen atoms = white. Credit: Carnegie Mellon

Caption: The X-ray crystallographic structure of the gold nanoparticle is shown. Gold atoms = magenta; sulfur atoms = yellow; carbon atoms = gray; hydrogen atoms = white.
Credit: Carnegie Mellon

Here’s a link to and citation for the paper,

Structural patterns at all scales in a nonmetallic chiral Au133(SR)52 nanoparticle* by Chenjie Zeng, Yuxiang Chen, Kristin Kirschbaum, Kannatassen Appavoo, Matthew Y. Sfeir, Rongchao Jin. Science Advances 20 Mar 2015: Vol. 1 no. 2 e1500045 DOI: 10.1126/sciadv.1500045

This paper appears to be open access.

* Link updated June 26, 2015.

Tel Aviv University and the quest for super-slim, bendable displays

It’s beginning to seem like the quest for the Holy Grail. That is, the search for an object more myth than fact, but researchers at Tel Aviv University (TAU) believe they are on the right track to develop a slim, flexible screen according to a March 30, 2015 news item on Nanowerk (Note: A link has been removed),

From smartphones and tablets to computer monitors and interactive TV screens, electronic displays are everywhere. As the demand for instant, constant communication grows, so too does the urgency for more convenient portable devices — especially devices, like computer displays, that can be easily rolled up and put away, rather than requiring a flat surface for storage and transportation.

A new Tel Aviv University study, published recently in Nature Nanotechnology (“Light-emitting self-assembled peptide nucleic acids exhibit both stacking interactions and Watson–Crick base pairing”), suggests that a novel DNA-peptide structure can be used to produce thin, transparent, and flexible screens. The research, conducted by Prof. Ehud Gazit and doctoral student Or Berger of the Department of Molecular Microbiology and Biotechnology at TAU’s Faculty of Life Sciences, in collaboration with Dr. Yuval Ebenstein and Prof. Fernando Patolsky of the School of Chemistry at TAU’s Faculty of Exact Sciences, harnesses bionanotechnology to emit a full range of colors in one pliable pixel layer — as opposed to the several rigid layers that constitute today’s screens.

A March 30, 2015 American Friends of Tel Aviv University news release, which originated the news item, describes the material’s advantages and how the researchers developed it,

“Our material is light, organic, and environmentally friendly,” said Prof. Gazit. “It is flexible, and a single layer emits the same range of light that requires several layers today. By using only one layer, you can minimize production costs dramatically, which will lead to lower prices for consumers as well.”

For the purpose of the study, a part of Berger’s Ph.D. thesis, the researchers tested different combinations of peptides: short protein fragments, embedded with DNA elements which facilitate the self-assembly of a unique molecular architecture.

Peptides and DNA are two of the most basic building blocks of life. Each cell of every life form is composed of such building blocks. In the field of bionanotechnology, scientists utilize these building blocks to develop novel technologies with properties not available for inorganic materials such as plastic and metal.

“Our lab has been working on peptide nanotechnology for over a decade, but DNA nanotechnology is a distinct and fascinating field as well. When I started my doctoral studies, I wanted to try and converge the two approaches,” said Berger. “In this study, we focused on PNA — peptide nucleic acid, a synthetic hybrid molecule of peptides and DNA. We designed and synthesized different PNA sequences, and tried to build nano-metric architectures with them.”

Using methods such as electron microscopy and X-ray crystallography, the researchers discovered that three of the molecules they synthesized could self-assemble, in a few minutes, into ordered structures. The structures resembled the natural double-helix form of DNA, but also exhibited peptide characteristics. This resulted in a very unique molecular arrangement that reflects the duality of the new material.

“Once we discovered the DNA-like organization, we tested the ability of the structures to bind to DNA-specific fluorescent dyes,” said Berger. “To our surprise, the control sample, with no added dye, emitted the same fluorescence as the variable. This proved that the organic structure is itself naturally fluorescent.”

The structures were found to emit light in every color, as opposed to other fluorescent materials that shine only in one specific color. Moreover, light emission was observed also in response to electric voltage — which make it a perfect candidate for opto-electronic devices like display screens.

Here’s a link to and a citation for the paper,

Light-emitting self-assembled peptide nucleic acids exhibit both stacking interactions and Watson–Crick base pairing by Or Berger, Lihi Adler-Abramovich, Michal Levy-Sakin, Assaf Grunwald, Yael Liebes-Peer, Mor Bachar, Ludmila Buzhansky, Estelle Mossou, V. Trevor Forsyth, Tal Schwartz, Yuval Ebenstein, Felix Frolow, Linda J. W. Shimon, Fernando Patolsky, & Ehud Gazit. Nature Nanotechnology (2015) doi:10.1038/nnano.2015.27 Published online 16 March 2015

This paper is behind a paywall but a free preview is available via ReadCube Access.

CRISPR gene editing technique and patents

I have two items about the CRISPR gene editing technique. The first concerns a new use for the CRISPR technique developed by researchers at Johns Hopkins University School of Medicine described in a Jan. 5, 2015 Johns Hopkins University news release on EurekAlert,

A powerful “genome editing” technology known as CRISPR has been used by researchers since 2012 to trim, disrupt, replace or add to sequences of an organism’s DNA. Now, scientists at Johns Hopkins Medicine have shown that the system also precisely and efficiently alters human stem cells.

“Stem cell technology is quickly advancing, and we think that the days when we can use iPSCs [human-induced pluripotent stem cells] for human therapy aren’t that far away,” says Zhaohui Ye, Ph.D., an instructor of medicine at the Johns Hopkins University School of Medicine. “This is one of the first studies to detail the use of CRISPR in human iPSCs, showcasing its potential in these cells.”

CRISPR originated from a microbial immune system that contains DNA segments known as clustered regularly interspaced short palindromic repeats. The engineered editing system makes use of an enzyme that nicks together DNA with a piece of small RNA that guides the tool to where researchers want to introduce cuts or other changes in the genome.

Previous research has shown that CRISPR can generate genomic changes or mutations through these interventions far more efficiently than other gene editing techniques, such as TALEN, short for transcription activator-like effector nuclease.

Despite CRISPR’s advantages, a recent study suggested that it might also produce a large number of “off-target” effects in human cancer cell lines, specifically modification of genes that researchers didn’t mean to change.

To see if this unwanted effect occurred in other human cell types, Ye; Linzhao Cheng, Ph.D., a professor of medicine and oncology in the Johns Hopkins University School of Medicine; and their colleagues pitted CRISPR against TALEN in human iPSCs, adult cells reprogrammed to act like embryonic stem cells. Human iPSCs have already shown enormous promise for treating and studying disease.

The researchers compared the ability of both genome editing systems to either cut out pieces of known genes in iPSCs or cut out a piece of these genes and replace it with another. As model genes, the researchers used JAK2, a gene that when mutated causes a bone marrow disorder known as polycythemia vera; SERPINA1, a gene that when mutated causes alpha1-antitrypsin deficiency, an inherited disorder that may cause lung and liver disease; and AAVS1, a gene that’s been recently discovered to be a “safe harbor” in the human genome for inserting foreign genes.

Their comparison found that when simply cutting out portions of genes, the CRISPR system was significantly more efficient than TALEN in all three gene systems, inducing up to 100 times more cuts. However, when using these genome editing tools for replacing portions of the genes, such as the disease-causing mutations in JAK2 and SERPINA1 genes, CRISPR and TALEN showed about the same efficiency in patient-derived iPSCs, the researchers report.

Contrary to results of the human cancer cell line study, both CRISPR and TALEN had the same targeting specificity in human iPSCs, hitting only the genes they were designed to affect, the team says. The researchers also found that the CRISPR system has an advantage over TALEN: It can be designed to target only the mutation-containing gene without affecting the healthy gene in patients, where only one copy of a gene is affected.

The findings, together with a related study that was published earlier in a leading journal of stem cell research (Cell Stem Cell), offer reassurance that CRISPR will be a useful tool for editing the genes of human iPSCs with little risk of off-target effects, say Ye and Cheng.

“CRISPR-mediated genome editing opens the door to many genetic applications in biologically relevant cells that can lead to better understanding of and potential cures for human diseases,” says Cheng.

Here’s a link to and citation for the paper by the Johns Hopkins researchers,

Efficient and Allele-Specific Genome Editing of Disease Loci in Human iPSCs by Cory Smith, Leire Abalde-Atristain, Chaoxia He, Brett R Brodsky, Evan M Braunstein, Pooja Chaudhari, Yoon-Young Jang, Linzhao Cheng and Zhaohui Ye. Molecular Therapy (24 November 2014) | doi:10.1038/mt.2014.226

This paper is behind a paywall.

Not mentioned in the Johns Hopkins Medicine news release is a brewing patent battle over the CRISPR technique. A Dec. 31, 2014 post by Glyn Moody for Techdirt lays out the situation (Note: Links have been removed),

Although not many outside the world of the biological sciences have heard of it yet, the CRISPR gene editing technique may turn out to be one of the most important discoveries of recent years — if patent battles don’t ruin it. Technology Review describes it as:

    an invention that may be the most important new genetic engineering technique since the beginning of the biotechnology age in the 1970s. The CRISPR system, dubbed a “search and replace function” for DNA, lets scientists easily disable genes or change their function by replacing DNA letters. During the last few months, scientists have shown that it’s possible to use CRISPR to rid mice of muscular dystrophy, cure them of a rare liver disease, make human cells immune to HIV, and genetically modify monkeys.

Unfortunately, rivalry between scientists claiming the credit for key parts of CRISPR threatens to spill over into patent litigation …

Moody describes three scientists vying for control via their patents,

[A researcher at the MIT-Harvard Broad Institute, Feng] Zhang cofounded Editas Medicine, and this week the startup announced that it had licensed his patent from the Broad Institute. But Editas doesn’t have CRISPR sewn up.

That’s because [Jennifer] Doudna, a structural biologist at the University of California, Berkeley, was a cofounder of Editas, too. And since Zhang’s patent came out, she’s broken off with the company, and her intellectual property — in the form of her own pending patent — has been licensed to Intellia, a competing startup unveiled only last month.

Making matters still more complicated, [another CRISPR researcher, Emmanuelle] Charpentier sold her own rights in the same patent application to CRISPR Therapeutics.

Moody notes,

Whether obvious or not, it looks like the patent granted may complicate turning the undoubtedly important CRISPR technique into products. That, in its turn, will mean delays for life-changing and even life-saving therapies: for example, CRISPR could potentially allow the defective gene that causes serious problems for those with cystic fibrosis to be edited to produce normal proteins, thus eliminating those problems.

It’s dispiriting to think that potentially valuable therapies could be lost to litigation battles particularly since the researchers are academics and their work was funded by taxpayers. In any event, I hope sanity reigns and they are able to avoid actions which will grind research down to a standstill.

The Analysis of Beauty; an email from William Hogarth

Given that William Hogarth has been dead for 250 years (1697 – 1764), it was bit startling to receive an email from him. For the record, he was announcing a sound installation that’s part of the ‘gap in the air; a festival of sonic art’ being held in Edinburgh (Nov. 15, 2014 – Feb. 14, 2015).

Hogarth’s (or the artists’ group known as ‘Disinformation’) installation is presenting (from the Feb. 6, 2014 email announcement),

“The Analysis of Beauty” by Disinformation

Talbot Rice Gallery
The University of Edinburgh
Old College
South Bridge
Edinburgh EH8 9YL
0131 650 2210

Reception + preview 12.30 (lunch-time) 15 Nov 2014
Sound installation 15 to 29 Nov 2014



#theanalysisofbeauty @talbotrice75

“The eye hath this sort of enjoyment in winding walks, and serpentine rivers, and all sorts of objects, whose forms, as we shall see hereafter, are composed principally of what I call the waving and serpentine lines. Intricacy in form, therefore, I shall define to be that peculiarity in the lines, which compose it, that leads the eye a wanton kind of chace, and from the pleasure that gives the mind, intitles it to the name of beautiful…” William Hogarth “The Analysis of Beauty” 1753

In 1753 the Georgian artist William Hogarth self-published his magnum-opus, “The Analysis of Beauty” – the book in which Hogarth expounded an aesthetic system based on analysing the virtues of the Serpentine, S-shaped, waving and snake-like lines. The Serpentine Line that William Hogarth discussed is identical to what modern nomenclature refers to as the sine-wave – the mathematical function whose geometry finds physical expression in oscillatory motion of musical strings, in pure musical notes, and in many phenomena of engineering, physics and communications science, signal processing and information technology.

In context of the architect William Playfair’s design for the Georgian Gallery at Talbot Rice, sonic and visual arts project Disinformation presents a minutely-tuned assemblage of pure musical sine-waves, which extend and extrapolate the visual aesthetics of Hogarth’s analyses, manifesting throughout the Georgian Gallery as a gently-hypnotic, immersive and dream-like sound-world. The installation is created using signals from laboratory oscillators, which manifest in-situ as standing-waves (the audio equivalent of stationary pond-ripples), through which visitors move as they explore and interact with the architectural acoustics of the exhibition space.

Here’s a video featuring a version of Disinformation’s ‘Analysis of Beauty’,

The Nov. 6, 2014 email announcement describes some of what you may have seen (if you’ve watched the video) and gives a summarized history for this installation,

“The Analysis of Beauty” sound installation is accompanied at Talbot Rice by the video of the same name, in which musical sine-waves are fed into and displayed on the screen of a laboratory oscilloscope. These signals visually manifest as a slowly rotating rope-like pattern of phosphorescent green lines, strongly reminiscent of the geometry of DNA. This earliest version of “The Analysis of Beauty” installation was exhibited at Kettle’s Yard gallery in Cambridge, in 2000, where the Disinformation exhibit was set-up alongside works by Umberto Eco, Marc Quinn and the artist project Art & Language, and directly alongside one of Francis Crick & James Watson’s earliest working-models of DNA.

Joe Banks offers a more comprehensive history in a post titled “Disinformation and “The Analysis of Beauty” A Project History“on the slashseconds.org website,

“The Analysis of Beauty” is an optokinetic sound and light installation, created by the art project Disinformation1 , which takes its title from the book of the same name written by the painter, engraver and satyrist William Hogarth in 1753. The installation was conceived in December 1999 and first exhibited in January 2000, in the “Noise” exhibition at Kettle’s Yard gallery (curated by Adam Lowe and by the Cambridge historian of science Professor Simon Schaffer)2 . “The Analysis of Beauty” was exhibited alongside work by artists Marc Quinn and Art and Language, semiotician and author Umberto Eco, and the Elizabethan polymath (mathematician, astronomer, geographer and occultist) John Dee. On account of the (subjective, but strong) similarity between the imagery produced by this installation and DNA, this work was (recent controversies notwithstanding) exhibited at Kettle’s Yard directly opposite one of Francis Crick and James Watson’s original models of DNA.

The entry does not appear to have been updated since 2007 at the latest.

Coincidentally or not, I received a Nov. 8, 2014 email announcement about an installation in Rennes (France) by an artist who seems to be associated with the ‘Disinformation’ group,

 “Babylone Electrifiée” Joshua Bonnetta + Disinformation

Exhibition continues until 22 Nov 2014

Le Bon Accueil – Lieu d’Art Contemporain
74 Canal Saint-Martin
35700 Rennes

The “Babylone Electrifiée” exhibition (image below) features “The Analysis of Beauty”, “National Grid” and “Blackout” (Sound Mirrors) by Disinformation, plus “Strange Lines & Distances” by Joshua Bonnetta

Here’ s the image,

[downloaded from http://bon-accueil.org/]

[downloaded from http://bon-accueil.org/]

You can find out more about

the ‘gap in the air: a festival of sonic art’ here

University of Edinburgh’s Talbot Rice Gallery exhibitions here

Le Bon Accuei exhibitions here

Joshua Bonnetta here

Happy Listening! And, to whomever came up with the idea of emails from William Hogarth, Bravo!

Physics, nanopores, viruses, and DNA

A June 17, 2014 news item on Azonano describes a project which could help scientists decode strands of DNA at top speeds,

Nanopores may one day lead a revolution in DNA sequencing. By sliding DNA molecules one at a time through tiny holes in a thin membrane, it may be possible to decode long stretches of DNA at lightning speeds. Scientists, however, haven’t quite figured out the physics of how polymer strands like DNA interact with nanopores. Now, with the help of a particular type of virus, researchers from Brown University have shed new light on this nanoscale physics.

“What got us interested in this was that everybody in the field studied DNA and developed models for how they interact with nanopores,” said Derek Stein, associate professor of physics and engineering at Brown [Brown University, US] who directed the research. “But even the most basic things you would hope models would predict starting from the basic properties of DNA — you couldn’t do it. The only way to break out of that rut was to study something different.”

A June 16, 2014 Brown University news release (also on EurekAlert), which originated the news item, describes the problems with nanopores,

The concept behind nanopore sequencing is fairly simple. A hole just a few billionths of a meter wide is poked in a membrane separating two pools of salty water. An electric current is applied to the system, which occasionally snares a charged DNA strand and whips it through the pore — a phenomenon called translocation. When a molecule translocates, it causes detectable variations in the electric current across the pore. By looking carefully at those variations in current, scientists may be able to distinguish individual nucleotides — the A’s, C’s, G’s and T’s coded in DNA molecules.

The first commercially available nanopore sequencers may only be a few years away, but despite advances in the field, surprisingly little is known about the basic physics involved when polymers interact with nanopores. That’s partly because of the complexities involved in studying DNA. In solution, DNA molecules form balls of random squiggles, which make understanding their physical behavior extremely difficult.

For example, the factors governing the speed of DNA translocation aren’t well understood. Sometimes molecules zip through a pore quickly; other times they slither more slowly, and nobody completely understands why.

One possible explanation is that the squiggly configuration of DNA causes each molecule to experience differences in drag as they’re pulled through the water toward the pore. “If a molecule is crumpled up next to the pore, it has a shorter distance to travel and experiences less drag,” said Angus McMullen, a physics graduate student at Brown and the study’s lead author. “But if it’s stretched out then it would feel drag along the whole length and that would cause it to go slower.”

The news release then goes on to detail a possible solution to the problem of why DNA translocation varies in speed. Answering this question about DNA translocation could lead to faster and more accurate nanopore sequencing,

The drag effect is impossible to isolate experimentally using DNA, but the virus McMullen and his colleagues studied offered a solution.

The researchers looked at fd, a harmless virus that infects e. coli bacteria. Two things make the virus an ideal candidate for study with nanpores. First, fd viruses are all identical clones of each other. Second, unlike squiggly DNA, fd virus is a stiff, rod-like molecule. Because the virus doesn’t curl up like DNA does, the effect of drag on each one should be essentially the same every time.

With drag eliminated as a source of variation in translocation speed, the researchers expected that the only source of variation would be the effect of thermal motion. The tiny virus molecules constantly bump up against the water molecules in which they are immersed. A few random thermal kicks from the rear would speed the virus up as it goes through the pore. A few kicks from the front would slow it down.

The experiments showed that while thermal motion explained much of the variation in translocation speed, it didn’t explain it all. Much to the researchers’ surprise, they found another source of variation that increased when the voltage across the pore was increased.

“We thought that the physics would be crystal clear,” said Jay Tang, associate professor of physics and engineering at Brown and one of the study’s co-authors. “You have this stiff [virus] with well-defined diameter and size and you would expect a very clear-cut signal. As it turns out, we found some puzzling physics we can only partially explain ourselves.”

The researchers can’t say for sure what’s causing the variation they observed, but they have a few ideas.

“It’s been predicted that depending on where [an object] is inside the pore, it might be pulled harder or weaker,” McMullen said. “If it’s in the center of the pore, it pulls a little bit weaker than if it’s right on the edge. That’s been predicted, but never experimentally verified. This could be evidence of that happening, but we’re still doing follow up work.

The new approach using a virus answered questions while leading to new insights and possibilities (from the news release),

A better understanding of translocation speed could improve the accuracy of nanopore sequencing, McMullen says. It would also be helpful in the crucial task of measuring the length of DNA strands. “If you can predict the translocation speed,” McMullen said, “then you can easily get the length of the DNA from how long its translocation was.”

The research also helped to reveal other aspects of the translocation process that could be useful in designing future devices. The study showed that the electrical current tends to align the viruses head first to the pore, but on occasions when they’re not lined up, they tend to bounce around on the edge of the pore until thermal motion aligns them to go through. However, when the voltage was turned too high, the thermal effects were suppressed and the virus became stuck to the membrane. That suggests a sweet spot in voltage where headfirst translocation is most likely.

None of this is observable directly — the system is simply too small to be seen in action. But the researchers could infer what was happening by looking at slight changes in the current across the pore.

“When the viruses miss, they rattle around and we see these little bumps in the current,” Stein said. “So with these little bumps, we’re starting to get an idea of what the molecule is doing before it slides through. Normally these sensors are blind to anything that’s going on until the molecule slides through.”

That would have been impossible to observe using DNA. The floppiness of the DNA molecule allows it to go through a pore in a folded configuration even if it’s not aligned head-on. But because the virus is stiff, it can’t fold to go through. That enabled the researchers to isolate and observe those contact dynamics.

“These viruses are unique,” Stein said. “They’re like perfect little yardsticks.”

In addition to shedding light on basic physics, the work might also have another application. While the fd virus itself is harmless, the bacteria it infects — e. coli — is not. Based on this work, it might be possible to build a nanopore device for detecting the presence of fd, and by proxy, e. coli. Other dangerous viruses — Ebola and Marburg among them — share the same rod-like structure as fd.

“This might be an easy way to detect these viruses,” Tang said. “So that’s another potential application for this.”

Here’s a link to and a citation for the paper,

Stiff filamentous virus translocations through solid-state nanopores by Angus McMullen, Hendrick W. de Haan, Jay X. Tang, & Derek Stein. Nature Communications 5, Article number: 4171 doi:10.1038/ncomms5171 Published 16 June 2014

This paper is behind a paywall.