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Category: biotech/medical – Page 2,653

What universities can learn from one of science’s biggest frauds

Gunsalus agrees that the Sato case highlights some of the problems with misconduct investigations, and says that if shortcomings emerge, further reviews may be needed. She suggests institutional panels should include external members and that officials should also use a standardized checklist to strengthen their processes. “There should be some way for journals, funders, patients and others to be assured of the credibility and thoroughness of university reviews,” says Gunsalus.

Detailed analysis of misconduct investigations into huge research fraud suggests institutional probes aren’t rigorous enough.

Sensitive scanning technology for low frequency nuclear point mutations in human genomic DNA

Knowledge of the kinds and numbers of nuclear point mutations in human tissues is essential to the understanding of the mutation mechanisms underlying genetic diseases. However, nuclear point mutant fractions in normal humans are so low that few methods exist to measure them. We have now developed a means to scan for point mutations in 100 bp nuclear single copy sequences at mutant fractions as low as 10–6.Beginning with about 10 human cells we first enrich for the desired nuclear sequence 10 000-fold from the genomic DNA by sequence-specific hybridization coupled with a biotin–streptavidin capture system. We next enrich for rare mutant sequences 100-fold against the wild-type sequence by wide bore constant denaturant capillary electrophoresis (CDCE). The mutant-enriched sample is subsequently amplified by high fidelity PCR using fluorescein-labeled primers. Amplified mutant sequences are further enriched via two rounds of CDCE coupled with high fidelity PCR. Individual mutants, seen as distinct peaks on CDCE, are then isolated and sequenced. We have tested this approach by measuring N-methyl–N ′-nitro–N-nitrosoguanidine (MNNG)-induced point mutations in a 121 bp sequence of the adenomatous polyposis coli gene (APC) in human lymphoblastoid MT1 cells. Twelve different MNNG-induced GC→AT transitions were reproducibly observed in MNNG-treated cells at mutant fractions between 2 × 10–6 and 9 × 10–6. The sensitivity of this approach was limited by the fidelity of Pfu DNA polymerase, which created 14 different GC→TA transversions at a mutant fraction equivalent to ~10–6 in the original samples. The approach described herein should be general for all DNA sequences suitable for CDCE analysis. Its sensitivity and capacity would permit detection of stem cell mutations in tissue sectors consisting of ~10 cells.

Google backs a bid to use CRISPR to prevent heart disease

Ever wonder why some fortunate people eat chips, don’t exercise, and still don’t get clogged arteries? It could be because they’ve got lucky genes.

Now Alphabet (Google’s parent company) is bankrolling a startup company that plans to use gene editing to spread fortunate DNA variations with “one-time” injections of the gene-editing tool CRISPR.

Heart doctors involved say the DNA-tweaking injections could “confer lifelong protection” against heart disease.

A self-assembled nanoscale robotic arm controlled by electric fields

Most nanoelectromechanical systems are formed by etching inorganic materials such as silicon. Kopperger et al. improved the precision of such machines by synthesizing a 25-nm-long arm defined by a DNA six-helix bundle connected to a 55 nm-by-55 nm DNA origami plate via flexible single-stranded scaffold crossovers (see the Perspective by Hogberg). When placed in a cross-shaped electrophoretic chamber, the arms could be driven at angular frequencies of up to 25 Hz and positioned to within 2.5 nm. The arm could be used to transport fluorophores and inorganic nanoparticles.

Science, this issue p. 296; see also p. 279

The use of dynamic, self-assembled DNA nanostructures in the context of nanorobotics requires fast and reliable actuation mechanisms. We therefore created a 55-nanometer–by–55-nanometer DNA-based molecular platform with an integrated robotic arm of length 25 nanometers, which can be extended to more than 400 nanometers and actuated with externally applied electrical fields. Precise, computer-controlled switching of the arm between arbitrary positions on the platform can be achieved within milliseconds, as demonstrated with single-pair Förster resonance energy transfer experiments and fluorescence microscopy. The arm can be used for electrically driven transport of molecules or nanoparticles over tens of nanometers, which is useful for the control of photonic and plasmonic processes. Application of piconewton forces by the robot arm is demonstrated in force-induced DNA duplex melting experiments.

Tardigrade DNA inserted into human cells gives them X-ray resistance

This is where it gets a little weird.

When the team treated human cells in culture with extract of tardigrade, the GFP-tagged proteins stuck to human DNA just like they stick to tardigrade DNA, and cheerfully started doing what they do best: tamping down oxidative stress. When X-rays hit human cells, they do two kinds of damage. X-rays can cause direct DNA strand breaks, which are mostly single-strand. When they strike water molecules, they can also excite them into producing reactive oxygen species, which also cause single-strand breaks. High enough doses of X-rays can cause double-strand breaks. The damage-suppressing protein Dsup went immediately to work on the culture of human cells, suppressing or repairing single-strand and double-strand breaks by about 40%.

Clearly this means we can consume water bears to gain their powers. The study authors remark that the gene portfolio of the tardigrade represents “a treasury of genes” to improve or augment stress tolerance in other cells. Plug-and-play genetics, anyone?

Harvard Scientists Make ‘Landmark’ Discovery in Synthesizing Anti-Cancer Molecules Found in Sea Sponges

Harvard and Japanese scientists say they’ve made a “landmark” discovery in cancer drug development. In a new study published Monday, they say they have finally found a way to synthesize in bulk a complex class of promising cancer-fighting molecules derived from sea sponges. Their new strategy has already helped speed up research into these molecules, including a planned clinical trial in humans.

Called halichondrins, the molecules were originally discovered by Japanese researchers in the mid-1980s in sea sponges. It became quickly apparent that they were capable of aggressively fighting tumors in both mice and lab dishes containing human cells, and in a way different from other existing treatments.

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