Crucial step in human DNA replication observed using fluorescent tags
A Pennsylvania State University research team led by Stephen J. Benkovic reported in an April issue of the journal eLife the discovery of some previously unknown details about human DNA replication. During the process, sliding clamps — ring-shaped proteins — are loaded onto the DNA strand, encircling it and anchoring polymerases to the DNA. “Without a sliding clamp, polymerases can copy very few bases at a time. But the clamp helps the polymerase to stay in place, allowing it to copy thousands of bases before being removed from the strand of DNA,” explains postdoc Mark Hedglin. This process requires the activity of a “clamp loader” that latches and unlatches the sliding clamps at key stages. Using the FRET method, the scientists observed the formation of holoenzymes consisting of the polymerase and accessory factors, as well as the key steps in the interactions between all these molecules.
Rutgers-UMDNJ integration nears
On July 1, a major transition will take place as Rutgers, The State University of New Jersey, and the University of Medicine and Dentistry of New Jersey combine forces under the new banner of Rutgers Biomedical and Health Sciences. Officials say the effort will bring together the rich history, talent and programs of each university to maximize the effectiveness of the state’s investment in education, research and health. RBHS will promote multidisciplinary research, dealing with major issues in biomedical sciences and engineering, global health and health policy, and patient care delivery.
Medical science may be the answer to budget woes, says Hood
Leroy Hood, president of the Institute for Systems Biology, wrote in an editorial in The Hill about the cuts to biomedical research funding, focusing on the impact this might have on the Human Genome Project and on thousands of groundbreaking projects. He suggests that this is not a wise step despite the desire to prioritize expenditures, because advances in medicine will not only revolutionize health care but also will decrease medical costs. P4 Medicine — medicine that is predictive, personalized, preventive and participatory — is a concept just a few steps away, Hood wrote, and something that “makes sense for society — and it makes sense for the economy.” Hood continued: “Let’s not be short-sighted or shortchange the future path of medicine. The payoff is too great to let it slip by.”
One drug to shrink all tumors?
A research team at the Stanford University School of Medicine led by Irving Weissman reported in a March issue of the Proceedings of the National Academy of Sciences that it had developed a treatment that could shrink or cure a variety of human cancers that had been transplanted into mice. The work was based on a previous discovery concerning CD47 levels in healthy versus leukemia cells. CD47 is a protein expressed on healthy blood cells as a marker that blocks the immune system from destroying the cells and is found in high quantities in all human primary tumors. Anti-CD47 molecules have been shown to activate macrophages to kill malignant cells in petri dishes. When researchers administered the drug to mice with human tumors transplanted into their feet, the tumors shrank and did not spread, and some mice went into remission. “We have enough data already,” says Weissman, “that I can say I’m confident that this will move to phase I human trials.”
Clinical trials in a dish
Researchers at Stanford University School of Medicine seeking to predict how a drug will affect heart function have developed a technique using patient-specific induced pluripotent stem cells. The study, reported in a March issue of the journal Circulation, used skin samples from people with or without inherited heart diseases, transformed them into IPS cells, and then differentiated them into beating myocytes. This approach enabled researchers to study the cells with greater accuracy than the hamster kidney or ovary cells genetically engineered to express a human cardiac ion channel that researchers have used in the past. The myocytes expressed the same ion channels as surgically isolated adult human heart tissues and also expressed abnormalities corresponding to the diseases seen in the patients from whom the samples were collected. “In these instances, our stem-cell-based testing platform is more sensitive and accurate than the current industry standard, which can lead to false negatives and false positives,” said Ping Liang, a co-lead author of the study. “As a result, it may be a better way to test medications in preclinical trials.”
Biological computer created at Stanford
A team of Stanford University engineers reported last month in the journal Science that it has created the first intracellular computer. The conceptual basis of this creation is similar to that of an electronic computer but with biology as the transcriptor controlling the flow of important proteins as they travel along a strand of DNA like electrons on a copper wire. “We’re going to be able to put computers inside any living cell you want,” said lead researcher Drew Endy. “Any place you want a little bit of logic, a little bit of computation, a little bit of memory — we’re going to be able to do that.” The cellular computers could prove a useful tool not only in studying various mechanisms by delivering true-false answers but also by counting and detecting abnormalities, warning of toxic threats and even programming cells to self-destruct.
Unraveling the molecular roots of Down syndrome
In the March 24 issue of Nature Medicine, researchers at the Sanford Burnham Medical Research Institute report on the role of the extra chromosome inherited in Down syndrome in altering the brain and the development of the body. Evidence points to a protein called sorting nexin 27, or SNX27, that keeps glutamate receptors — important in learning, memory and behavior — on neuron membranes. It appears that chromosome 21 encodes the production of high quantities of a particular micro RNA, miR-155, whose increases correlate to proportionally lower levels of SNX27. Using a noninfectious virus to deliver new human SNX27 in the brains of Down syndrome mice, “first we see the glutamate receptors come back, then memory deficit is repaired,” said Xin Wang, a graduate student in Xu’s lab and first author of the study.
Turning skin into brain
A newly discovered method to turn skin cells into oligodendrocytes is giving hope to those seeking treatments for demyelinating diseases. In a study reported in the journal Nature Biotechnology, scientists at Case Western Reserve University School of Medicine took skin cells and obtained stem cells or fetal material from them. They then increased the intracellular levels of certain proteins known to be expressed in large quantities in oligodendrocyte progenitor cells, leading to the formation of myelin producing cells. These were functional when transplanted into myelin-deficient mice, making up for the defect. “The myelin repair field has been hampered by an inability to rapidly generate safe and effective sources of functional oligodendrocytes. The new technique may overcome all of these issues by providing a rapid and streamlined way to directly generate functional myelin producing cells,” said co-author Robert Miller.
Nanokicking stem cells to open for new generation of orthopedics
A unique, multidisciplinary team of scientists is studying the effects of nanovibrations on bone regeneration using a technique called laser interferometry, which also is used to detect ripples in space-time caused by gravitational waves. The procedure is based on the observation that individual bone cell membranes vibrate when they adhere to one another, encouraging cellular communication and promoting bone formation. Evidently, this vibration can be replicated in the lab by “kicking” the stem cells 1,000 times a second. Matt Dalby from the Centre for Cell Engineering at the University of Glasgow says, “This new observation provides a simple method of converting adult stem cells from the bone marrow into bone-making cells on a large scale without the use of cocktails of chemicals or recourse to challenging and complex engineering.” This discovery could be converted into improved therapies to stimulate bone formation and to maintain bone health in patients with orthopedic conditions.
This news roundup was compiled by ASBMB Today contributor Teodora Donisan (firstname.lastname@example.org), a medical student at Carol Davila University in Bucharest, Romania. Send links of interest to email@example.com for possible inclusion in future issues.