Cyagen Biosciences

Invariably, everyone gets old. However, as a true testament to human stubbornness, research toward a “cure” for aging has never stopped. Over the past few decades, various approaches have allowed scientists to generate animal models with extended lifespans. In recent years, this trend has moved from lower organisms to mammalian model systems. There are now several rodent models with enhanced longevity. Many of these models are directly relevant to human aging. A new study has identified a deletion in exon 3 of human growth hormone receptor (GHR) to be prevalent in naturally long-lived men (1). The presence of two copies of this mutation may allow men to live about ten years longer than they otherwise would. This agrees with many findings from rodent models. Transgenic mice that overexpress GH age rapidly, while knockout mice lacking GHR are long-lived (2,3). In humans and mice, IGF1 signaling is also closely linked to longevity via a signaling pathway overlapping that of GH (4,5).

Introduction: Reduced heart function due to aging and disease is a major health problem. Heart attacks can have devastating impacts, often leading to the death of the patient or chronic morbidity for those that survive. A major reason for the sensitivity of the circulatory system to heart malfunction is that heart muscle cells (cardiomyocytes) of adult mammals generally do not divide. This means that when a cardiomyocyte dies, due to localized loss of blood supply, for example, that dead cell will never be replaced. Normally, heart tissue has a robust, healthy blood supply, but when a heart attack strikes, portions of heart tissue are deprived of blood flow, resulting in rapid cell death in those sections of the heart. Recovering the ability to heal Interestingly, newborn hearts can heal. In 2011, scientists discovered that newborn mice are able to regenerate cardiomyocytes to repair heart damage, but this ability is lost soon after birth (1). More recently, researchers disc

It has long been known that cells acquire mutations over time. In fact, ongoing random mutation rates are such that no two cells in a human body are identical. Unlike most cell types, which die and are frequently replaced, human neurons can live for decades, carrying on their functions for the entire lifetime of the organism. We know that mutations must accumulate in neurons over their long lifespan, but until now we had no clear picture of the frequency or pattern of neuronal mutations. Using the seemingly impossible approach of sequencing genomes of individual human brain cells, a group of researchers have now shown that the average human neuron carries a whopping 1700 mutations per neuron. These neuroscientists, based at Harvard and MIT, sorted individual neurons from the postmortem brains of three individuals, amplified their genomic DNA, and were able to use whole-genome sequencing to obtain individual cell genome sequences at ~40x coverage. In addition to the sheer number of neur

A major goal of synthetic biology is to design and build digital genetic circuits inside cells, effectively programming cellular functions. Achieved this could allow living cells to be engineered to perform decision-making tasks, similar to computers, but composed of genetic elements rather than electronic components. This technology could be applied to medical therapeutics, molecular detection, diagnostics, tissue engineering, bio-electronic interfaces, and many other science-fictionesque uses. However, genetic elements tend to be less predictable and more “leaky” than electronic components, and this has limited progress. In a brand-new study from the University of Washington, Gander et al. overcame these obstacles by using CRISPR/Cas9 linked to the transcriptional repressor Mxi1 to make genetic circuits in yeast. The group designed and built a library of single-gene NOR gates (which give an output signal only when there are no input signals). Each gate consists of a gRNA-expressing

Introduction: Optogenenetics refers to a family of techniques which allow modulation of biological processes using light. Over the past 12 years, optogenetics has revolutionized neuroscience and is now expanding to impact many fields of biology. There are now genetic tools which can be used for photo-control of signal transduction, gene expression, apoptosis, histone modification, cytoskeletal dynamics, and many more processes. The incredible power of optogenetics comes from the very high spatial and temporal resolution possible using light, as opposed to chemical or genetic effects. Optogenetics can also be combined with other genetic or chemical approaches to further increase the level of experimental control. For example, optogenetic constructs can be targeted to specific cell types or subcellular locations, or can be engineered to require specific chemical cofactors, further limiting when and where light-induced effects will occur. The key component of an optogenetics ex

Introduction: For complex diseases like multiple sclerosis (MS), animal models are highly important because they allow researchers to systematically study numerous factors which contribute to the disease in ways that are not possible in human patients. Animal models also serve as testing arenas for potential treatments. However, the disease complexity which makes animal models so necessary also means that animal models are only able to reflect some aspects of human MS. Induced Models Experimental autoimmune encephalomyelitis (EAE) is the oldest model of demyelinating diseases (1), and has led to the discovery of human therapies for MS, but EAE has shortcomings that make it difficult to connect findings from the animal model to the human disease, particularly with respect to drug testing (2). To induce EAE, researchers stimulate a T-cell-mediated immune response against myelin, which leads to an inflammatory response in the CNS, and demyelination. Not only is the pathophysiology o

Viruses are pseudo-living organisms which inhabit and influence virtually every type of plant and animal cell. In some contexts, viral infection has obvious and profound consequences for the host organism, such as causing disease. However, many viral infections go completely unnoticed, with infections having essentially no phenotype or having an effect only long after the initial infection. Several examples of chronic, unnoticed viral infections affecting human health have been discovered. In several cases these long-term effects have been implicated in major, worldwide health problems. Cytomegalovirus (CMV) is one of the most common human virus, being present in around 75% of adults worldwide. Once acquired, CMV infection persists lifelong in a dormant state. CMV infection is a known risk factor for high blood pressure and has been implicated in atherosclerosis, and people who test positive for human CMV infection are at increased risk of cardiovascular diseases and heart attack

The advent of CRISPR-mediated genome-editing has revolutionized the generation of genetically modified animal models. In the few short years since its introduction, CRISPR has played a pivotal role in numerous animal model studies. In the past, genetic studies in mice have primarily relied on gene knockouts and knockins made using ES cells. In contrast to the labor-intensive ES cell methods, CRISPR/Cas9 approaches can now produce knockouts, knockins or Large-fragment Knockin with less effort. This new technology has led to a flood of activities by the research community in making CRISPR-based mouse models. Although CRISPR off-target effects have been a concern, researchers have tried to mitigate this concern by predicting potential CRISPR off-target sites based on homology to the target site, and then sequencing these potential off-target sites in CRISPR-treat mice to confirm their intactness1-3. Based on these analyses, it is generally assumed that CRISPR off-target effects are v

In many ways, regeneration is the ‘holy grail’ of medical research. To be able to completely heal from injuries and to regrow lost organs or tissues is a feat that most mammals are generally not capable of. However, many types of animals can regenerate to varying degrees, and some mammalian tissues do normally display regenerative capabilities. Studying model organisms has provided some insight into the biochemical pathways that allow regeneration in certain systems, as well as mechanisms that prevent regeneration in others. Here are a couple of recent studies which could represent major breakthroughs in regeneration research. Epigenetic barriers prevent regeneration in the eye   In adult mammals, the retina is almost completely incapable of regeneration. In contrast, bony fish can regenerate retinal tissue lost due to injury. The process of retinal regeneration in fish requires the generation of new neurons from Müller glial cells within the eye, driven by the activity of the pron

On Thanksgiving Day, many of you may gather together with family around a table adorned with a turkey. In a grocery store or on a farm, turkeys are remarkably uniform, but wild turkeys have remarkably diverse appearances and behaviors. One striking example of this is the decorative displays of male (or “tom”) turkeys, which includes iridescent feathers, a brightly colored head and neck, and enlarged beard, caruncles, wattle and snood. These features are used to attract females, but surprisingly many toms don’t mate, and these subordinate males actually look and act different from dominant males. Once dominance is established within a family of toms, subordinate turkeys develop less vivid coloration and smaller wattles, caruncles and snoods. These turkeys help their one dominant brother to attract mates, and serve as bodyguards to fight off other groups of males, but the subordinate toms don’t attempt to mate. The basis for the existence of these two male phenotypes is a f

Approximately 30 per cent of patients with epilepsy do not respond to anti-epileptic drugs. In these cases, all neurologists can do is attempt to find the right combination of medication through trial and error. A treatment that could target the root cause of epilepsy is a beacon of hope for these patients. But identifying the cause of the pathology is no easy feat. "There are many genes involved," said Jacques Michaud, pediatrician at CHU Sainte-Justine and Professor of Pediatrics and Neuroscience at the Faculty of Medicine of Université de Montreal. "Each child can have different genetic mutations. Often the clinical symptoms do not clearly reflect the cause of epilepsy, which makes choosing the right treatment more difficult." A recent study by Michaud examining 200 children with epileptic encephalopathy - epilepsy combined with intellectual or overall developmental disability - and their parents could lead to the development of a more rational anti-epilepti

Stem cells taken from muscle tissue could promote better blood flow in patients with diabetes who develop peripheral artery disease, a painful complication that can require surgery or lead to amputation. A new study in mice at the University of Illinois found that an injection of the stem cells prompted new blood vessels to grow, improving circulation in the affected tissues and function in the affected limbs. The stem cells also induced changes in gene expression in the surrounding tissues, prompting the release of factors to reduce inflammation and increase circulation. The study was published in the journal  Theranostics . "PAD is very common in diabetic patients, but it is difficult to diagnose because patients experience symptoms when the disease is already at an advanced state," said study leader Wawrzyniec Lawrence Dobrucki, a professor of bioengineering and of medicine and head of the Experimental Molecular Imaging Laboratory at the Beckman Institute for Adv

A U of G researcher is the first to discover the type of stem cell that is behind the gecko's ability to re-grow its tail, a finding that has implications for spinal cord treatment in humans. Many lizards can detach a portion of their tail to avoid a predator and then regenerate a new one. Unlike mammals, the lizard tail includes a spinal cord. Prof. Matthew Vickaryous found that the spinal cord of the tail contained a large number of stem cells and proteins known to support stem cell growth. "We knew the gecko's spinal cord could regenerate, but we didn't know which cells were playing a key role," said Vickaryous, lead author of the study recently published in the  Journal of Comparative Neurology . "Humans are notoriously bad at dealing with spinal cord injuries so I'm hoping we can use what we learn from geckos to coax human spinal cord injuries into repairing themselves." Geckos are able to re-grow a new tail within 30 days -- faste

Young adults dependent on marijuana and alcohol are less likely to achieve adult life goals, according to new research by UConn Health scientists presented November 5 at the American Public Health Association 2017 Annual Meeting & Expo. UConn Health researchers examined data from the Collaborative Study on the Genetics of Alcoholism (COGA) to track the effect teenage alcohol and marijuana use has on the achievement of life goals, defined as educational achievement, full time employment, marriage and social economic potential. The study includes 1,165 young adults from across the United States whose habits were first assessed at age 12 and then at two-year intervals until they were between 25 and 34 years old. Most of the study participants had an alcoholic grandparent, parent, aunt or uncle. Overall, individuals who were dependent on either marijuana or alcohol during their teen years achieved lower levels of education, were less likely to be employed full time, were less like

A new method for acquiring viable cells from cryopreserved tissue samples could provide researchers with a model for collecting and analyzing samples from different study sites to conduct more centralized research, according to new research findings presented this week at the 2017 ACR/ARHP Annual Meeting in San Diego. Rheumatoid arthritis (RA) is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men. The Accelerating Medicines Partnership (AMP) program's RA/SLE Network aims to discover new, more effective ways to treat the inflammatory response that causes these chronic diseases by identifying the cell types and signals central to driving inflammation in RA patients. Before the program's researche

Each of your cells contains two copies of 23 chromosomes, one inherited from your father and one from your mother. Theoretically, when you create a gamete -- a sperm or an egg -- each copy has a 50-50 shot at being passed on. But the reality isn't so clearcut. Scientists have observed that chromosomes can "cheat," biasing the chance that they will make it into a sex cell. Now, a team from the University of Pennsylvania has shown how this bias arises in female cells. With careful observation and experiments with mouse oocytes, the precursors of eggs, they've detected molecular signals that create an asymmetry in the machinery that drives meiosis, the cell-division process that gives rise to gametes. Certain chromosomes, the researchers found, exploit this asymmetry to move themselves over to the "right" side of a cell during division and wind up in the egg. By casting light on a common yet poorly understood facet of meiosis, the findings may lead to a

Researchers at Memorial Sloan Kettering Cancer Center in New York City and Massachusetts Institute of Technology in Boston have developed a new, three-step system that uses nuclear medicine to target and eliminate colorectal cancer. In this study with a mouse model, researchers achieved a 100-percent cure rate--without any treatment-related toxic effects. The study is reported in the November featured article in  The Journal of Nuclear Medicine . Until now, radioimmunotherapy (targeted therapy) of solid tumors using antibody-targeted radionuclides has had limited therapeutic success. "This research is novel because of the benchmarks reached by the treatment regimen, in terms of curative tumor doses, with non-toxic secondary radiation to the body's normal tissues," explains Steven M. Larson, MD, and Sarah Cheal, PhD, of Memorial Sloan Kettering Cancer Center. "The success in murine tumor models comes from the unique quality of the reagents developed by our group,