The Bacteria that are Good for Us

Chains of StreptococciSalmonella. Streptococcus. Shigella. The most well-known bacteria are those that cause disease. Our relationship with them is one of combat. With good reason, we look for ways to avoid encountering them and to eliminate them when we do meet.

But not all bacteria are bad for us. Of course we have known for years that we are colonized by harmless bacteria, but recently, studies on the human microbiome have revealed many surprising things about these bacterial tenants. Studies are showing that the teeming multitudes of organisms living in and on the human body are not just harmless bystanders, but complex, interrelated communities that can have profound effects on our health.

Three studies published last week in Science add more to the growing body of microbiome surprises, showing that certain gut bacteria are not only good for us, but may even be required for the effectiveness of some anti-cancer immunotherapies.

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ISHI 28 Workshop: Towards Better Solutions for Body Fluid Identification

Although techniques for DNA analysis of forensic samples have evolved considerably in recent years, the methods used to identify particular body fluids in forensic casework have remained relatively unchanged over the same time period. This year, one of the workshops offered at the International Symposium on Human Identification (ISHI; to be held in Seattle from October 2-5), will be focused on current and emerging techniques for body fluid identification that promise change—applying molecular genetics and proteomics analysis to the problem of body fluid identification.

According to the ISHI conference website, the purpose of the workshop is to “highlight current serology methods using critical case examples while also exploring emerging methods that could complement or replace these traditional techniques”. Continue reading

Five Ways to Explain CRISPR Without Delivering a Lecture

Recently a FaceBook friend of mine (who is not a scientist) shared a video from WIRED Science where the concept of CRISPR is explained at 5 Levels of Difficulty— for a 7 year old, a teenager, a college student, a grad student and a CRISPR expert.

First it was pretty amazing to me that my non-scientist friends are interested enough in learning about CRISPR to share this type of information—perhaps showing just how popular and exciting the method has become. People outside the scientific field are hearing a lot about it, and are curious to know more.

This video does a great job of explaining the technique for all its intended audiences. It also is a nice illustration of how to share information in an easily understandable format. Even with the 7 year old and 14 year old, the information is shared in a conversational way, with everyone involved contributing to sharing information about CRISPR.

Really nice. Here’s the WIRED video:

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NanoBiT Assay Applied to Study Role of SOD1 in ALS

NanoBiT Protein ComplementationBack in 2015 the Ice Bucket Challenge brought Amyotrophic Lateral Sclerosis (ALS) to public attention, initiating worldwide pleas for more funding of research toward a cure for this fatal disease, which is characterized by progressive degeneration of motor neurons. In spite of many efforts over the last few decades, the precise cause of ALS is still unknown.

The complexity of the problem of ALS pathogenesis is highlighted in the review “Decoding ALS: from genes to mechanism”  published in Nature in November 2016. The review highlights a long list of genetic factors implicated in ALS, grouping them into genes affecting protein quality control, RNA stability/function, and the cytoskeletal structure of neuronal cells.

Mutations in the antioxidant enzyme superoxide dismutase (SOD1) were the first to be associated with ALS. According to the review, more than 170 SOD1 mutations causing ALS have since been identified. Many of these mutations are thought to result in misfolding of SOD1, contributing to toxicity when the misfolded protein accumulates within the cell.

A paper by Oh-hashi et al., published in Cell Biochemistry and Function in October 2016 used the NanoBiT protein complementation assay to investigate the effect of two common ALS-associated SOD1 mutations on dimerization of the SOD1 protein. Continue reading

It must be Christmas, the BMJ is funny

Every year the British Medical Journal publishes a Christmas edition—a delightful confection of whimsical articles that apply the rigor of the scientific method to such topics as “The survival time of chocolates on hospital wards” or “Dispelling the nice or naughty myth—A retrospective observational study of Santa Claus”.  Much of the delight of these articles is in the details of the tongue-in-cheek tone, the accompanying figures, traditionally crafted methods sections and satisfyingly obvious conclusions. For example, did you know that “sleep deprived people appear less healthy, less attractive, and more tired compared with when they are well rested”, or that the “survival time of a chocolate on a hospital ward is short, at under an hour, and that the initial rate of chocolate consumption from a box is rapid but slows with time”? (It’s those hard ones no-one likes that are left at the end.)

Last week saw the publication of the 2016 BMJ Christmas edition featuring such topics as the effect of Pokémon GO on physical activity among young adults (short term value), and “Open toe Sandals Syndrome”—a study attempting to answer the question “Is fear of summer foot exposure contributing to the workload of mycology labs?” 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

Previewing ISHI 27: Mitochondrial DNA Analysis in Forensic Investigations

Credit: National Institutes of Heath, USA

Mitochondrial DNA has important implications for forensic analysis. Image Credit: National Institutes of Heath, USA

The 27th annual International Symposium on Human Identification—ISHI 27—will be held September 26-29 in Minneapolis, MN. One of the largest conventions focused on forensic DNA analysis, ISHI features presentations on the latest advances, interesting cases and key issues relevant to the field. In anticipation of this years’ conference, here is a preview of one talk, provided by Dr. Mitchell Holland of Penn State University (Dr. Holland will also be participating in the June 28 TechTour in New York). The focus of Dr. Holland’s research is mitochondrial DNA (mtDNA) analysis and its application to human identification. At ISHI, he will be presenting his recent work using NextGen sequencing to analyze mtDNA heteroplasmy.

mtDNA heteroplasmy was key to identifying the remains of Tsar Nicholas II

mtDNA heteroplasmy was key to the identification of the remains of Tsar Nicholas II

Heteroplasmy is the presence of more than one mitochondrial genome within an individual. Perhaps the most famous example of the effect of mtDNA heteroplasmy on a forensic investigation is the identification of the remains of Tsar Nicholas II. mtDNA from bones discovered in a mass grave in 1991, was identical in sequence to known relatives of the Tsar except at one position, where there was a mixture of matching (T) and mismatching (C) bases. Lingering doubt caused by this result meant that confirmation of the authenticity of the remains was delayed. Ultimately mtDNA analysis provided the needed evidence for identification, showing that the same heteroplasmy was present in mtDNA extracted from bones of the Tsar’s brother, confirming the Tsar’s identity (Ivanov et al., (1996) Nature Genetics 12(4), 417-20).

Here is what Dr. Holland had to say about the work he will present at ISHI: Continue reading

Two light stories for Friday

For this Friday blog, here’s a sampling of two recent papers highlighting use of the small, bright, NanoLuc luciferase in interesting ways.

Bioluminescence-based hormone:receptor binding studies

A review by Ya-Li Liu and Zhan-Yun Guo, published this week in Amino Acids summarizes recent work of the authors and others using NanoLuc luciferase labeled protein/peptide hormones in receptor binding assays. Typically, studies assessing binding of hormones to receptors have used radioactive tracers. The brightness of NanoLuc luciferase makes bioluminescence an attractive alternative as a sensitive and safer option. Because cell membrane receptors are difficult to purify in quantity, the amounts available for experiments are usually limited. Therefore, tracers used in binding assays need to have a high affinity for the receptor, must not interfere with binding, and must be highly sensitive. Continue reading

Zika: Another RNA Virus Emerges

no mosquitoZika virus has been in the news recently due to growing concerns about its global spread. If you have never heard of Zika virus before, you are not alone. Although first discovered in the 1940s, Zika has not been the subject of much study as infection is considered rare and the symptoms mild. However, all this has changed in recent months due to the rapid spread of the virus in Latin America, where it has been associated with an increased incidence of microcephaly, a severe birth defect where babies are born with underdeveloped brains. Although the connection of Zika with microcephaly is not yet proven, the circumstantial evidence is strong, leading the World Health Organization to declare the spread of Zika virus an international public health emergency earlier this week. Continue reading

Unexpected connections: Gut bacteria influence immunotherapy outcomes

Over the last few years, human microbiome studies have revealed fascinating connections between our colonizing microorganisms and ourselves—including associations between gut bacterial populations and obesity, disease susceptibility, and even mood. The relationship between us and our microbial colonists—once considered completely benign, is now being revealed as an intricate, complicated partnership with the potential to redefine who “we” are in fundamental ways.

Two papers published back-to-back in the November 27 issue of Science add further to this growing body of knowledge—reporting a new and unexpected connection between gut bacterial species and the effectiveness of cancer immunotherapies in mice. The work suggests one reason why such treatments are effective in some circumstances, but not others. Both papers report that the presence of specific bacterial populations may be required for the efficacy of certain treatments, and raise the intriguing question “Could the composition of bacteria in the gut be manipulated to enhance the effectiveness of cancer treatments?” Continue reading