Profiling Pseudouridine

  • Two New Methods for Sequencing Pseudouridine Leverage Old Chemistry
  • New Methods Reveal ‘Rewiring’ of Genetic Code by Post-Transcriptional Pseudouridination
  • Exciting Future for New Analytical Methods for Modified mRNA
  • Be Sure to Read the Very End of the Blog for a Special Offer!

At the risk of seeming enamored with pseudouridine, which I previously proclaimed—with justifications—to be The 2014 Modified Nucleobase of the Year, recent reports about this fascinating base lead me now to feature it here once again. In that past post, it was pointed out that uridine, which is incorporated into all RNA during transcription of genomic DNA, differs from pseudouridine—historically abbreviated by the Greek symbol Ψ –by how one nitrogen (shown in red below) switches place with a carbon for bonding to the ribose ring. It was also noted that this switch has been long known to be carried out after transcription (aka post-transcriptionally) by an enzyme called—appropriately—pseudouridine synthase, the exact mechanistic details for which remain controversial. This post-transcriptional process that converts U to Ψ at specific positions in RNA is called pseudouridination.
Continue reading

Nanopore Sequencing: 20 Years On 

  • Once Only a Dream, Nanopore Sequencing is Now Reality
  • Oxford Nanopore Technologies MinION Sequencer Apps Spotlighted  
  • Fully Automated Sample Prep and Higher Throughput Coming Soon
Dream Messenger oil painting by Leszek Andrzej Kostuj with nanopore-like eyes. Taken from

Dream Messenger oil painting by Leszek Andrzej Kostuj with nanopore-like eyes. Taken from

I don’t really know who first dreamt the exciting idea of moving DNA through a nanometer-sized pore to read sequence as electronic blip-like signals, but lots of folks are glad that someone did because this seemingly impossible dream is now reality.

My initial close encounter with this almost alien idea—pun intended—happened in 1998 when I first read about it in a patent by George Church (my recent blog-pick as The Most Interesting Scientist in the World), David Deamer, Daniel Branton, and others jointly assigned to Harvard and the University of California. This patent was filed 20 years ago on March 17, 1995 so St. Patrick’s Day should share with what I hereby suggest as annual Nanopore Sequencing Day.
Continue reading

RNA Vaccines: Safer and Better Than Pathogens

  • Polio Virus Accidentally Discharged by GlaxoSmithKline  
  • Anthrax Accidentally Shipped to Numerous Labs
  • New RNA Vaccines are Viewed as Much Safer and Better

Polio Virus Accidental Discharge

Polio virus is pretty but highly pathogenic. Taken from

Polio virus is pretty but highly pathogenic. Taken from

The genesis of this blog about safer, better vaccines using RNA instead of pathogenic organisms was an incident that received very little attention in the US but was big news in Europe and—frankly—scared the bejeezus out of me. London-based GlaxoSmithKline (GSK) acknowledged in a report that its vaccine production personnel in Belgium dumped 12 gallons of liquid contaminated with poliovirus into the local sewage treatment plant and subsequently into the Lasne River. Yikes!

A spokesman is quoted as saying that there was “an accidental discharge of cleaning solution that had been used to sanitize equipment used in the manufacture of polio vaccine.” However, chances of anyone developing polio from being exposed to the water were said to be very low, “given the high level of dilution and high level of public vaccination”—vaccination against polio is compulsory in Belgium. That may be true, but the issue is increasing safety, as you’ll see from what follows here.

Continue reading

What is This Hot New Field of Electronic Sequencing?

  • New Technology is Literally and Figuratively Hot
  • Stanford-incubated Startup has Patent for Semiconductor-based Sequencing Using Proton or Heat Detection
  • Sizzling Hot Promises Draw Stellar Scientific Advisor Board and World Renown Venture Capitalists

Truth be told, I’ve been an avid follower—if not addicted technophile—of next-generation sequencing (NGS) ever since the 1990s when inventive researchers—fueled by NIH grant-dollars—dreamed of displacing ABI’s then dominant fluorescent-based (aka BigDye® terminator) DNA sequencing systems. Assessing proposed technology of this would-be-competition was in fact part of my job at ABI back then. At the time, ABI was selling hundreds of millions of dollars of its sequencing instruments and reagents into the then rapidly emerging—if not exploding—field of genomics. So, you didn’t need an MBA from Harvard to conclude that any company that could commercialize significantly “faster, better, cheaper” sequencing would find instant marketability and might achieve even higher revenues.

Continue reading

Nutraceuticals—Grow Your Own (GYO) Medicines?

  • Broccoli Bred into Cholesterol Lowering Food
  • Oz: Wizard or Quack?
  • Are the FDA and FTC Overwhelmed or Underperforming?  

‘Let food be thy medicine and medicine be thy food,’ said Hippocrates, Greek physician in the fifth century BC in Athens, known as the father of western medicine. Now, in the 21st century, researchers are putting their own spin on the saying by investigating ways to incorporate medicinal compounds in our food.


Taken from

Taken from

You may recall one of my recent posts expounding the apparent therapeutic effects of broccoli in treating symptoms of Autism, specifically the benefits of sulforaphane, the naturally occurring compound thought to be the active component. Well, broccoli is once again taking center stage in a technically related and more on-point example just announced by researchers at the University of Reading in the UK. This study involved breeding a variety of broccoli containing 2-3x more glucoraphanin (which is converted in the body to sulforaphane) than usual and claims that the resulting broccoli reduces cholesterol.

Continue reading

RNA in DNA—Mistake or Mystery?

  • Human DNA Misincorporates >1,000,000 Ribonucleotides Per Replication Cycle
  • These Mistakes are Likely Biological Mysteries
  • Four New Sequencing Methods May Demystify Why There’s “R in DNA”

When I came across a publication on the presence of RNA in DNA my initial reaction, frankly, was great surprise, if not outright disbelief. As the so-called “blueprint” of life, I reckoned that DNA is virtually sacred in terms of its chemical composition, albeit subject to base mutations as well as insertions and deletions of sequence. In other words, I had heretofore been under the impression that DNA’s repeating units are 100% deoxyribonucleotide (and conversely that RNA’s are ribonucleotides), thus giving DNA (and RNA) the eponymous name is has. So, I thought to myself, if that’s reportedly not the case for DNA, what are the facts and implications, i.e., is RNA in DNA just a rare “mistake” or is this yet another example of a “mystery” of Nature. Below is what I’ve learned about this revelation.
Continue reading

Holy Toledo! What’s In Your Tap Water May Be Toxic!

  • Toxins from Harmful Algae Blooms (HABs) Shut Down Toledo’s Drinking Water Supply
  • Fertilizer Run-off is to Blame, Along with Global Warming
  • Beware of Dead Zones that Result from HABs

While the origin of the now-not-trendy exclamation “Holy Toledo!” is subject to much speculation, the origin of a deadly toxin in the water supply for Toledo, Ohio last year is quite clear: algae growing in Lake Erie near the city’s water intake system. Having grown up in Buffalo, NY located at the opposite end of Lake Erie, which is the 4th largest lake in the U.S., I can still clearly remember seeing this algae as seemingly endless greenish muck. I also remember gagging from its stench, wondering when something would be done to stop it. That was many years ago, and sadly this situation still persists and has led to a real crisis in water contamination, as well as created massive areas of water ominously called “dead zones.” After you read the following short synopsis of these troublesome problems, you may want to forego drinking tap water in favor of pure glacier water—while it lasts (but that’s a whole other scary story about global warming that we’ll save for another time).
Continue reading

Three Fascinating Facts about Epigenetics

  • You Are What Your Father Eats
  • Exercise Affects Epigenetics
  • There’s an Epigenetic Clock

Before getting to some truly fascinating—in my opinion—facts about epigenetics, I thought it would be worth briefly explaining the essence of epigenetics to get us in sync. Many similar but differently worded definitions of epigenetics have been proposed over the years; however, I favor this one, which a group of experts hashed out at venerable Cold Spring Harbor Laboratory—and published, together with their detail reasoning:

“An epigenetic trait is a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence.”

Continue reading

Gene-Expression Biomarkers Can Detect Depression

  • First-ever Lab Test for Depression Found Using RT-PCR
  • FDA Approval as Diagnostic Possible by Early 2016
  • Huge Potential Market as 1-in-10 US Adults Suffer from Depression

While it’s normal for everyone to occasionally feel blue or sad, prolonged bouts of depression that interfere with normal life are indicative of a serious mental health issue. While there are numerous forms and differing severity of depressive disorders, as described at a National Institute of Mental Health (NIMH) website, only two factual aspects of this illness really stand out in my opinion:

Redder countries have higher depression rates. Bluer countries have lower depression rates. Taken from The Washington Post.

Redder countries have higher depression rates. Bluer countries have lower depression rates. Taken from The Washington Post.

  • Depression is a very common illness. The Centers for Disease Control and Prevention estimates that 1-in-10 US adults suffer from depression, which reportedly costs close to $50B annual in lost productivity in the work place. Globally, more than 350 million people of all ages are afflicted with depression, according to recent statistics from the World Health Organization (WHO). By the year 2020, WHO estimates that depression will be the second leading cause of “lost years of healthy life”, following heart disease. Incidentally, as seen from the map below, depression rates around the world vary significantly among countries.
  • Depression is diagnosed based on the patients’ self-report of their symptoms and the evaluation of one or more structured psychiatric interviews with the patient by a psychiatrist, psychologist or primary care physician. The absence of direct, non-subjective measures of depression can lead to relatively lengthy time-to-treatment, non-reporting, or—sorry to say—fraudulent claims and/or treatments based solely on what is said as opposed to what is objectively measured.
Bi-polar Depression © Mena Purdy oil on canvas.

Bi-polar Depression © Mena Purdy oil on canvas.

Continue reading

The Most Interesting Scientist in the World: George M. Church

  • Mind Boggling Breadth and Significance of Scientific Publications
  • Serial Entrepreneur and Science Advisor to Many Companies
  • Radical Advocate of Total Openness for Personal Genomics

While seeing for the umpteenth time a Dos Equis beer commercial featuring The Most Interesting Man in the World, I was suddenly inspired to write a blog about The Most Interesting Scientist in the World. After scrolling and polling my memory to decide who that would be, it was an easy decision to pick George M. Church, professor of genetics at Harvard. As I’ll briefly highlight herein, Prof. Church’s contributions continually span a mind boggling spectrum of science that cuts across academic theory, ground breaking “how to” methods, serial entrepreneurship, and—perhaps most importantly—radical openness for personal genomics.

George M. Church and The Most Interesting Man in the World: ‘I don’t always read science, but when I do it’s by George M. Church.’ (taken from Bing Images)

Continue reading