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From Skin to Eggs

May 18, 2017

Now that grades are turned in, I can take a moment off from the Indivisible site that’s occupied my blogging since November, to highlight a momentous event, long foreseen: Conversion of skin cells to eggs. For the first time, molecular biologists have converted mouse fibroblasts (a type of skin cell) into pluripotent stem cells (cells that have lost the skin-type specialization) which then were converted into egg cells. The eggs were then fertilized in vitro (IVF) with normal sperm, and produced viable mouse pups.

For humans they say skin-to-egg is maybe five years away. If every skin cell could be a baby, will we outlaw dandruff?

The details are more intriguing yet, as describe by Katsuhiko Hayashi in his original report.

The full process actually required two types of cells: embryonic stem cells (providing helper genes), and the skin cell-derived stem cells to become eggs. The requirement of embryonic helpers is one aspect that will prove challenging to perform in humans.

For egg production, the two types of cells are aggregated to form ovary-like tissues, “ovaries in a dish.” Within these artificial ovaries, the skin-cell derived cells differentiate (become specialized) to form functionally normal oocytes (egg cells). Remarkably, the egg cells undergo normal development including exclusion of one set of chromosomes within a tiny polar body. The successful fertilization rate is about

The study’s author describes further implications of their work here. The timing of human egg production will involve several months, and the requirement for supporting embryonic cells is a hurdle. But in the past such requirements for stem cell procedures have been superseded by chemical treatments that mimic the cells’ developmental signals.

What medical applications could this technique have, if developed in humans? Such techniques might lead to uniparental humans (the egg and sperm derived from one person); or to humans with multiple parents providing different chromosomes. One thing is clear, the role of conception in human biology would be shifted, with unknowable results for our concept of what is human.

Microbes of 2016

December 30, 2016

From Syria to Trump Tower, this year has not been the greatest for human beings. Yet our microbial communities have flourished. Even the White House (perhaps with prescience) announced the National Microbiome Initiative, predicting that microbes would accomplish some of the year’s most noble and memorable achievements–from CRISPR/CAS (bacterial antiviral defense applied to human gene editing) to the ancient invention of multicellular life. We can all appreciate that one; or regret it, as the case may be. My own lab has been a romp through bacteria reversing our drug resistance, to Haloarchaea evolving for Mars. Why send Mars our humans, when we can send our microbes?

One last salute to microbial scientists: What’s lurking in your showerhead? As you might guess, recalling our famous old shower curtain, the answer is, quite a crowd. Robb Dunn’s lab works at identifying microbes and meiofauna (microscopic invertebrates) in all parts of your home, from your undusted furniture to the antiperspirant of your armpit. Perhaps most intriguing is the great Showerhead Microbiome Project.

Do you ever unscrew the cap of your showerhead to find out what’s growing inside? Not very often. Yet you use the showerhead every day. A daily inoculation–just like all our evolution projects at Bacteria Lab Kenyon. You are running a lifelong evolution project, with your self as culture medium. All you need to do is swipe your scalp now and then, run a DNA prep, and send the contents to MR DNA.

Alternatively, you can send your showerhead water to Dunn Lab project. They plan to sample showerheads from “around the United States and Europe”–rather parochial, I suppose, but they might be persuaded to expand.

So what might we expect to find in the showerhead community? One quaint hypothesis is that we might find amebas, gobbling up the “nontuberculous mycobacteria” (the ones that don’t cause TB but do infect immunocompromised people). More prosaically, we might just find assorted pollen grains from pines and cedars. An early finding of Dunn Lab: the fungi in your home depend more on geography, whereas your home’s bacteria come from you. You may recall the microbial air print–that we can now identify who’s been in a room based on the bacteria they left in the air.

After showerheads, you can move on to the Sourdough Project. Find out the real reason different bakers make different tasting bread. (Hint: Do you have earwax?)

From our own microbiome to yours, we wish you all a Happy New Year.


Ross Sea: Protecting Antarctica

November 6, 2016

While some of us up North endure elections and Brexits, down under in  Australia the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR) has been busy protecting one of Antarctica’s great treasures, the Ross Sea.

CCAMLR is a commission of 36 nations founded in 1982  to protect Antarctica and preserve this continent for science and future generations. This monumental agreement is all the more remarkable when you consider the size of Antarctica (larger than the USA) and the lousy state of the year 1982 (height of Reagan and AIDS). This commission has largely succeeded in protecting Antarctica from mining and harvesting operations. It has allowed the National Science Foundation (backed by unobtrusive US military forces) to largely administer access for biology, geology, and climate science.

But off the coast, it’s been another story, with fishing and whaling threatening the ecosystems of the Southern Ocean. This week, however, CCAMLR has reached agreement to put off limits an enormous swath of ocean known as the Ross Sea.

The Ross Sea is familiar as the region I crossed in the C-17 cargo hold on our way to McMurdo Station. McMurdo sits on the lava spit of Ross Island; in the above map, located at the edge of the ice shelf just below the words “Ross Sea Shelf.” The edge of the ice shelf is a magical region attracting thousands of penguins, seals and killer whales. On our final helicopter flight back from Taylor Valley, the pilot dipped and buzzed the shelf, startling pods of Adelies, Emperors and others for our last good look. The new CCAMLR agreement will protect more than a million and a half square kilometers of this ecosystem.

Meanwhile, back at Kenyon our own bit of Antarctica in our -80 freezer is yielding up secrets to the science of our supercomputer. Current projects include:

  • Discovering life forms capable of living half the year at forty below (where centigrade equals Fahrenheit)
  • Mining the microbial genomes for enzymes that make new antibiotics
  • Growing purple bacteria that store sunlight as hydrogen fuel–a stowaway colony from the mat stuff we picked up off the ice.


Nose Snot Antibiotic

October 8, 2016


Usually we look for antibiotics in exotic places such as Antarctica, aiming to find new drugs that no human pathogen has ever seen. But what if an antibiotic could be hiding in plain sight–or nearer yet, up your nose?

That’s what Alexander Zipperer and colleagues found, at the University of Tübingen. They focused on a pathogen Staphylococcus aureus, cause of serious skin infections including drug-resistant varieties such as methicillin-resistant Staph (MRSA). But S. aureus  has a surprising ability to hang out up the nose of healthy, unsuspecting carriers–that’s about one in three of us. Look to your right, then your left: One of you three’s got it.

So what keeps some of us healthy, despite this pathogen? The German researchers proposed there might exist some other nose-loving bacterium, part of our nasal snot microbiome–some bacterium that defends us from the bad ones. To find this white-knight defender, the researchers screened a collection of previously isolated nasal bacteria, cultured on a synthetic nasal medium (i.e. standardized snot). They tested individual isolates by dropping each culture upon a lawn of the tester strain Staph aureus. One isolate Staphylococcus lugdunensis showed a clear halo, a region where the tester Staph failed to grow.

The new S. lugdunensis was shown to produce a novel antibiotic, which they named lugdunin. Lugdunin (above) is a nonribosomal peptide; like vancomycin, the antibiotic is formed by a factory-modular enzyme that generates peptide bonds. Unlike ribosomal proteins, however, the nonribosomal peptide can contain all kinds of amino acids, beyond the canonical twenty. Lugdunin actually includes a thiazolidine, a unique five-membered ring including a sulfur atom.

So we may have a new antibiotic; or even a new probiotic, in the form of S. lugdunensis to inoculate our noses.


Tasmanian Devils Fight Cancer

September 17, 2016

The Tasmanian Devil is today’s largest known marsupial mammal; which is not saying much, barely two feet long aside from tail. Hunted to extinction, these tiny fierce predators remain today on the island of Tasmania. They form extended social networks, fighting, mating, and eating entire carcasses down to the bone–a tidy habit that actually endears them to Tasmanian farmers. Considered an iconic symbol and attractor of tourists to Tasmania, the devil now enjoys the benefits of the Australian government’s Save the Tasmanian Devil Program.

Like most charismatic mammals, the devil’s main enemy for survival has long been considered the humans who hunted them to near extinction. But in recent years, devils face an even more horrible foe: transmissible facial tumors, known as devil facial tumor disease (DFTD). First seen in 1996, the tumors disfigure the face in horrible ways that I prefer not to show here, but you can find them all over the internet. What is unusual about these tumors is that the cancerous tissue actually transmits like a pathogen to other animals, typically during fighting, which the little carnivores spend a lot of time doing. Why does the cancer spread? Apparently because the devil populations have such low diversity that their immune systems fail to recognize the tumor cells as foreign. The tumor spreads so fast that most devils get infected and eventually die of organ failure or starvation. Overall the population has declined by 90%.

Will the devil go extinct? Surprisingly, the answer appears to be no. A new study by an international research team, including Brendan Epstein and Andrew Storfer from Washington State U, focuses on a few isolated populations of devils that seem to be holding their own (pink disks below). This map (Figure 1) shows the steady advance of the disease across Tasmania, and the sites of surviving populations.



The authors of the study reasoned that any devil populations having survived the near-100% fatality rate of DFTD must have undergone selection for specific gene mutations that confer resistance to the tumors. Sure enough, the animals’ sequenced genomes reveal fascinating mutations.

In the genomes, seven DNA regions were found that showed high frequency for particular alleles (variant versions of a gene). These regions are “known to science” because they share similarity with the DNA of all mammals, who share a common ancestor. Five of these seven regions encode proteins that are associated with cancer prevention or the immune system, as studies in other mammals. For example, protein CD146 is known as “melanoma adhesion molecule.”  This protein functions in normal cell cycle and adhesion (attachment to other cells) as well as regulation of the immune system that prevents cancer. Another protein is known as a “proto-oncogene,” that is, a gene that can mutate to cancer–but ordinarily protects from cancer. Presumably, the mutant version of these proteins somehow protects the individual devils from the tumors that came close to exterminating them.

The authors title their work, “Rapid Evolutionary Response to a Transmissible Cancer in Tasmanian Devils.” The case shows an unusually sped up version of the evolutionary arms race that faces all living things; how to out-live that which threatens survival and reproduction. The recent finding is good news for devils–and may also shed light on cancer prevention in related species, including our own.


Smart as a Duck

July 24, 2016


Is a duckling capable of abstract thought?
Somehow this story of true intelligence got buried beneath the convention news.

According to authors in the journal Science, experiments demonstrate the ability of newly hatched duckling to distinguish the concepts “same” and “different.”

Previously, the authors note, “pigeons and bees can be trained to discriminate whether novel images contain humans or not, or whether novel paintings are by Monet or Picasso.” Such discrimination requires extensive training between specific patterns–the pattern of a “human” shape, versus other; or the patterns of Monet versus Picasso. The discrimination of paintings does not imply artistic talent; in fact, the animals might be observing something trivial, such as the color scheme or size of objects depicted. These previous findings all required concrete objects to discriminate.

But can we demonstrate learning of an abstract concept?

Authors Antone Martinho III and Alex Kacelnik, of the Oxford Zoology department, claim to have done just that. They made ingenious use of a powerful memory tool: the imprinting of birds on their parent. Imprinting has long been demonstrated as an introductory lab in biology. The student waits for a duck egg to hatch; then the first thing the hatchling sees or hears is the student. Forever after, the hatchling follows the student as if they were its mother.

If ducklings can imprint upon a human student, what about inanimate objects? Or even an abstract concept?

In the experiment, newly hatched ducklings were exposed to pairs of objects.

In some cases, the hatchlings were exposed to pairs of objects that were identical. Other hatchlings were presented with pairs of objects that differed in shape or color.

After exposure, the hatchlings were then presented with a pair of objects of a different kind (balls versus cones). But two kinds of presentation were done: of two different objects, or two identical objects. For example, a duck was imprinted on “two spheres”, then tested on “two cones” (identical) or on “cube plus tower” (different). The duck’s preference was then measured by the number of times it stepped toward the object pair. Even though the new objects were of a different kind, the ducks still preferred (stepped toward) an identical pair, if it had imprinted on an identical pair; or a dissimilar pair, if it had imprinted on a dissimilar pair. The experiment worked either for shape or color.

When picked up by the canonical alien abductors, I wonder how many of us humans could pass this test.


Peacock Spiders Revisited

July 9, 2016

For something more cheerful, here’s a return of the Peacock Spider. Apparently seven new species of peacock spider have been discovered in Australia. The discovery was reported in the journal Peckhamia–a journal devoted to the biology of jumping spiders. Clearly a sign of the growing overproliferation of specialty journal, but in this case we can’t complain too much.

The Peckham society is a treasure trove of fascinating and diverse spider behavior, such as this one feasting on a fellow spider. Not the same species, so it doesn’t count as cannibalism (unless you’re a cannibal for eating a cow.)

And for the truly insatiable spider enthusiast, check out the Peckham’s video collection. To think that all this variety represents one small branch of the arachnid tree–It’s enough to give some hope for Earth’s biological world.