CRISPR: Gene Editing and Movie Madness

There are new developments in genetics coming to light every day, each with the potential to dramatically change life as we know it. The increasingly controversial gene editing system, dubbed CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats), is at the root of it all. Harnessed for use in genome editing in 20131, CRISPR has given hope to researchers looking to solve various biological problems. It’s with this technology that researchers anticipate eventually having the means to genetically modify humans and rid society of genetic disorders, such as hemophilia. While this is not yet possible, the building blocks are steadily being developed. Most recently, two groundbreaking studies concerning CRISPR have been released to the public. Continue reading

Predicting the Future with Dirty Diapers

Microbiome research is booming right now, with more and more evidence that our personal health and environment are shaped and influenced by the microbes we harbor and encounter. One area of study I find particularly interesting is how the microbiome we acquire at birth affects our long-term health.

A flood of new findings have emerged related to infant microbiome research, leaving parents like me scratching their heads about whether the secrets to our children’s future health may exist in the seemingly endless stream of dirty diapers we change.

The human microbiome evolves and develops in utero and then during and after delivery is colonized by bacteria encountered during exposure to the external environment. The initial composition of microbes an infant is populated with influences their lifelong microbiome signature and can be influenced by many factors along the way, including the microbiome community of the mother, use of antibiotics or other antibacterial substances, breastfeeding, C-section birth. These variables have been correlated with disruption of the infant microbiome and associated with differences in cognitive development and the development of disease, such as asthma and allergies.

In general, these correlations are discovered by taking a fecal sample from an infant and analyzing the DNA sequences of the bacteria present. The microbiome composition of the individual is then compared against different individual characteristics (such as presence or absence of a disease) at the time of the sample and/or at later points in time. Finally researchers look for statistically significant patterns among individuals with similar characteristics or microbiome communities. This type of study can reveal associations between the microbiome and individual traits, but further experiments are needed to show causation. Continue reading

Preventing Viral Infection by Blocking Cellular Receptors with a Tethered Antibody

Cross section of mature HIV. Copyright David S. Goodsell, The Scripps Research Institute.

Cross section of mature HIV. Copyright David S. Goodsell, The Scripps Research Institute.

Finding a way to neutralize or block infection by HIV has long been pursued by viral researchers. Various treatments have been developed, driven by the need to find effective drugs to manage HIV in infected individuals. The ultimate goal is to develop a vaccine to prevent HIV from even taking hold in the body. With all of our knowledge about the cellular receptors HIV needs to enter the cell, there has to be a method to prevent a viral particle from binding and being internalized. Many researchers are pursuing neutralizing antibodies to the virus as one method. What about antibodies that target the cellular receptor recognized by the virus? In a recently published article in Proceedings of the National Academy of Sciences, antibodies to cellular receptors for rhinovirus and HIV were tethered to the plasma membrane and tested for the ability to prevent infection. Continue reading

Gut Microbes and Hypertension: Demonstrating a Causal Link

Most of us are aware that the human body is covered by and full of microorganisms. And we understand that most of these microorganisms are helpful, both in terms of competition with and protection against invading microorganisms, and in the gut, as agents of digestion.

Bacillus subtilis, an example of Firmicutes, and not a good gut microbe. By Y tambe (original uploader) - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=49528

Bacillus subtilis, an example of Firmicutes, and not a good gut microbe. By Y tambe (original uploader) – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=49528

In the past decade, however, research has brought compelling details implicating gut microbes in obesity, cancer, insulin resistance and such central nervous system disorders as depression, austism spectrum disorder and multiple sclerosis (Adnan, S. et al.). Yet the mechanisms and details of these associations have not been fully demonstrated.

Gut bacteria have been proven to be connected to thickening of heart vasculature, known as atherosclerosis. Researchers have demonstrated that bacteria metabolize choline and L-carnitine from food to trimethylamine, which crosses the gut barrier into circulation and reaches the liver. In the liver, trimethylamine is metabolized to the atherogenic molecule triethylamine-N-oxide (Gregory, J.C. et al., Brown and Hazen). These studies are among the few that provide a direct connection between gut microbes and a pathological condition. Continue reading

Weaving Tangled Webs with Cell-Free DNA

The ability to isolate and assay circulating cell-free DNA from plasma holds promise for improved diagnostics and treatment in the clinic. The use of blood-based non-invasive prenatal testing (NIPT) has been well described. Such testing is based on circulating cell-free fetal DNA in blood of a pregnant woman for diagnosis and screening  of chromosomal anueploidy (e.g. Trisomy 21, Down Syndrome), sex-linked diseases, and genetic diseases that are known to result from a specific mutation in a single gene (1). Additionally, most cancers carry somatic mutations that are unique to the tumors, and dying tumor cells release small pieces of their DNA into the blood stream (2). This circulating cell-free tumor DNA can be used as a biomarker to “follow” cancer progression or regression during treatment, and diagnostic methods also are being developed to detect even early stage cancers from circulating tumor DNA (3). Further, increases in circulating cell-free DNA have been well documented after intense exercise, trauma, sepsis and even associated with autoimmune diseases such as system lupus erythematosus (SLE; 1,4). In these latter examples increases in extracellular DNA are associated with evolutionarily conserved innate immune responses involving the production of neutrophil extracellular traps (NETs). Monitoring the circulating cell-free DNA of NETs has implications for treatment and diagnosis of autoimmune diseases, cardiovascular events and traumatic injuries (4–7).

How Neutrophils Weave a Defensive Web

Blood smear showing two prominent neutrophils in the field of view

Blood smear showing two prominent neutrophils in the field of view

Neutrophils are the most abundant type of white blood cell and are part of the innate immune response, participating in non-specific immune responses to injury or pathogens. They are one of three types of granuolcytes, and can be recognized by their multi-lobed nucleus and the prominent granules that fill their cytoplasm. Generally they are first to the scene of injury or infection. Early in my scientific career, I was taught that neutrophils fought disease via phagocytosis and occasionally by firing a barrage of toxic enzymes and molecules at invaders. Mostly though they released cytokines that recruited the “important” cells of the specific immune system to the area.

For these reasons, I never really thought much about neutrophils. That is until recently, when I learned about Neutrophil Extracellular Traps (NETs). It turns out that neutrophils are pretty awesome, sacrificing themselves in a cloud-like explosion of DNA, chromatin, and granule proteins Continue reading

Of Elephant Research and Wildlife Crime – Molecular Tools that Matter

Here at Promega we receive some interesting requests…

Take the case of Virginia Riddle Pearson, elephant scientist. Three years ago we received an email from Pearson requesting a donation of GoTaq G2 Taq polymerase to take with her to Africa for her field work on elephant herpesvirus. Working out of her portable field lab (a tent) in South Africa and Botswana, she needed a polymerase she could count on to perform reliably after being transported for several days (on her lap) at room temperature. Through the joint effort of her regional sales representative in New Jersey/Pennsylvania (Pearson’s lab was based out of Princeton University at the time) and our Genomics product marketing team, she received the G2 Taq she needed to take to Africa. There she was able to conduct her experiments, leading to productive results and the opportunity to continue pursuing her work. Continue reading

The Birth of a Disease? A New Anthrax-Like Disease Found in Sub-Saharan Africa

It usually starts with one; one dead animal, one sick individual, one case that a doctor thinks is unusual. These are all ways that a new disease makes its presence known. In the case of Bacillus cereus biovar anthracis, it started with a dead chimpanzee (1).  

The wild western chimpanzee was found dead in Côte d’Ivoire in 2001. An investigation led by scientists from the Robert Koch Institute in Berlin identified the pathogenic cause of death to be an atypical B. cereus isolate that caused an anthrax-like disease. Continue reading

Digging Up More Clues in the History of the Black Death

Bubonic plague victims in a mass grave in 18th century France. By S. Tzortzis [Public domain], via Wikimedia Commons

Bubonic plague victims in a mass grave in 18th century France. By S. Tzortzis [Public domain], via Wikimedia Commons

My last blog post on the Black Death highlighted research that suggested that the reintroduction of Yersinia pestis, the causative agent of the pandemic, originated in Europe during the 14–18th centuries rather than from Asia, the hypothesized origin. In my post, I wrote about my curiosity regarding what an Asian skeleton positive for Y. pestis from that same time period would reveal about the strain or strains that were circulating. Well, a team of researchers has been exploring the issue of strain circulation and an Asian connection, and recently published what they gleaned from additional historic Y. pestis samples in Cell Host & Microbe.

Teeth from 178 individuals in three different locations (two European, one Asian) were screened for Y. pestis infection using the plasminogen activator (pla) gene. Continue reading

Magnetic Bacteria Carry Drugs into Tumors

cancer cellAt first glance, the biology of magnetic, underwater-dwelling, oxygen-averse bacteria may seem of little relevance to our most pressing human health problems. But science is full of surprises. A paper published this week in Nature Nanotechnology presents an inspired use of these bacteria to deliver anti-cancer drugs to tumors, specifically targeting the oxygen-starved regions generated by aggressively proliferating cells. Continue reading

An Epizootic for the Ages: Revisiting the White-Nose Syndrome Story

Map showing the spread of WNS across North America

Map showing the spread of WNS across North America

In March 2016, two hikers on a trail east of Seattle, WA, found a little brown bat lying on the ground in obviously poor condition. The bat was taken to an animal shelter where it died two days later from White-Nose Syndrome (WNS).

This bat was the first case of WNS found west of the Rocky Mountains. It represented a jump in the spread of WNS, and a troubling one. WNS was first detected in a cave in Albany, New York, and since then it has been moving slowly westward at a rate of about 200 miles per year, according to David Blehert of the United States Geological Survey, the laboratory that confirmed the WNS diagnosis for the Washington bat. Before this year’s discovery outside of Seattle, the westward-most case detected was in eastern Nebraska.

WNS, caused by a cold-loving fungus, Psuedogymnoascus destructans (Pd), can kill 100% of the hibernating bats in a colony, and in the ten years since it has been detected and monitored has killed over 6 million bats in the United States and Canada. As of July 2016, bats infected with the fungus have been found in 29 states and 5 Canadian provinces.

According to Blehert, this is probably the “most significant epizootic of wildlife” ever observed; never before have we seen hibernating mammals specifically affected by a skin fungus. What does that mean? Are we looking at extinction for some bat species? What are the ecological consequences of rapidly losing so many individuals to disease so quickly? And, what, if anything, can be done to combat the disease and help bat populations recover? Continue reading