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Archive - Mar 2, 2017

Powerful & Flexible Software (CRISPETa) Developed for Designing Quick & Easy CRISPR Deletion Experiments

Until recently, genomics was a “read-only” science. But scientists, led by Dr. Rory Johnson at the University of Bern and the Centre for Genomic Regulation in Barcelona, Spain, have now developed a tool for quick and easy deletion of DNA in living cells. This software will boost efforts to understand the vast regions of non-coding DNA, or “Dark Matter,” in our DNA and may lead to discovery of new disease-causing genes and potential new drugs. Genomics is the field of research studying how our genome, or entire DNA sequence, specifies a human being, and how errors in this sequence give rise to diseases. Genomics was recently a “read-only” endeavor: researchers used powerful technology to read genome sequences and their regulatory layers. However, until recently, there was no way to edit or delete DNA for either basic research objectives, or for potential therapeutic interventions. Just a few years ago, this outlook changed dramatically with the discovery of a revolutionary technique for editing genomes: “CRISPR-Cas9.” CRISPR-Cas9 is a molecular tool composed of two simple components: a molecular barcode, called “sgRNA,” which is designed by the researcher to recognize one precise location in the genome; and a protein, Cas9, that binds to a structured loop in the sgRNA. By introducing these two units, researchers may perform a wide range of operations on specific pieces of genomic DNA, from introducing small mutations, to regulating gene activity, to tagging the DNA with small sequences. Until recently, most studies employing CRISPR-Cas9 were aimed at silencing protein-coding genes, the best-studied part of our genome. However, 99% of our genome consists of DNA that does not encode any protein.

Intestinal Bacteria of Irritable Bowel Syndrome (IBS) Patients Alter Gut & Brain Function in Mice; Finding May Lead to New Microbiota-Directed Therapies for GI Upset & Brain Disorders

Research from McMaster University and the University of Waterloo, both in Canada, has found that bacteria in the gut impact both intestinal and behavioral symptoms in patients suffering from irritable bowel syndrome (IBS), a finding which could lead to new microbiota-directed treatments. The new study, published in the March 1, 2017 issue of Science Translational Medicine, was led by researchers from the Farncombe Family Digestive Health Research Institute at McMaster--Drs. Premysl Bercik and Stephen Collins--in collaboration with researchers from the University of Waterloo. The article is titled “Transplantation of Fecal Microbiota from Patients with Irritable Bowel Syndrome Alters Gut Function and Behavior in Recipient Mice.” IBS is the most common gastrointestinal disorder in the world. It affects the large intestine and patients suffer from abdominal pain and altered bowel habits like diarrhea and constipation, which are often accompanied by chronic anxiety or depression. Current treatments aimed at improving symptoms have limited efficacy because the underlying causes are unknown. The goal of the study was to explore whether fecal microbiota from human IBS patients with diarrhea have the ability to influence gut and brain function in recipient mice. Using fecal transplants, researchers transferred microbiota from IBS patients with or without anxiety into germ-free mice. The mice went on to develop changes both in intestinal function and behavior reminiscent of the donor IBS patients, compared to mice that were transplanted with microbiota from healthy individuals.

Scientists Create Artificial Mouse “Embryo” from Stem Cells

Scientists at the University of Cambridge in the UK have managed to create a structure resembling a mouse embryo in culture, using two types of stem cells - the body's “master cells” - and a 3D scaffold on which the cells can grow. Understanding the very early stages of embryo development is of interest because this knowledge may help explain why more than two out of three human pregnancies fail at this time. Once a mammalian egg has been fertilized by a sperm, it divides multiple times to generate a small, free-floating ball of stem cells. The particular stem cells that will eventually make the future body, the embryonic stem cells (ESCs), cluster together inside the embryo towards one end: this stage of development is known as the blastocyst. The other two types of stem cell in the blastocyst are the extra-embryonic trophoblast stem cells (TSCs), which will form the placenta; and the primitive endoderm stem cells that will form the so-called yolk sac, ensuring that the fetus's organs develop properly and providing essential nutrients. Previous attempts to grow embryo-like structures using only ESCs have had limited success. This is because early embryo development requires the different types of cell to coordinate closely with each other. Now, however, in a study published online on March 2, 2017 in Science, University of Cambridge researchers describe how, using a combination of genetically-modified mouse ESCs and TSCs, together with a 3D scaffold known as an extracellular matrix (ECM), they were able to grow a structure capable of assembling itself and whose development and architecture very closely resembled the natural mouse embryo.

Humans Found to Have Three Times More Brown Fat Than Previously Thought; Obesity & Diabetes Drugs That Activate Brown Fat May Be More Effective Than Initially Believed; Creatine Clearance Shown to Affect Brown Fat Activity

Compared to white fat, brown body fat burns through energy at an extraordinary rate. However, until now the proportion of brown fat in humans was thought to be quite small. Now a study conducted by researchers at the Technical University of Munich (TUM) in Germany has shown: The quantity of brown fat in humans is three times greater than previously known. As a consequence, new obesity and diabetes drugs that activate brown adipose tissue are expected to be more effective. For the study, published in the Journal of Nuclear Medicine, nearly 3,000 PET scans of 1,644 patients were analyzed. PET is an acronym for positron emission tomography, a method widely used in oncology. PET scans enable the visualization of metabolic activity in the body. Because a tumor often has a different energy metabolism than healthy tissue, PET scans can be used to demonstrate the presence of metastases. "A byproduct of PET scans is that they allow us to see active brown adipose tissue," said Dr .Tobias Fromme from the Else-Kröner-Fresenius Center at the TUM. “Brown adipose tissue absorbs lots of sugar, and we can observe this activity through the scans." For example, it is conceivable that a drug could reduce excessive blood sugar levels in diabetics by increasing the activity of the brown fat. Similarly, it is conceivable that patients with obesity could use the high rate of energy combustion through brown fat to melt away their excess weight -- at least to a certain extent. "In any event, the outlook for the efficacy of drugs in brown adipose tissue can be adjusted upwards," said the researcher. The analysis of the PET scans also revealed that some groups of persons have an easier time activating their brown fat than others, or even have more of it in the first place.