Jellyfish gettin’ it on, baby

This is too much verisimilitude. The movie below is of the mating behavior of the jellyfish Carybdea sivickisi, and the first thing you’ll notice is that the scientists have set it to good old classic porn music.

The second thing you’ll notice, that I found annoying, is that they used too high a power objective to film it, so everything is jerking everywhere and none of the participants stay in the field of view for any length of time. Why is it that porn is afflicted with so many gynecological close-ups? Come on, set the mood, show us whole individuals instead of fragmented zooms of body parts.

Hawaii’s shame

This is shocking news, but not too surprising: I know a few of the people in this facility, and when I talked to them last they were deeply concerned about this possibility. The University of Hawaii is planning to shut down the Kewalo Marine Laboratory. They’re doing it so they can funnel more money into the expansion of a cancer research center, which is certainly valuable, but not at the expense of closing half of their marine facilities. This is especially shocking because heck, when students here in the cold and land-locked midwest talk to me about going into marine biology, many of them ask about Hawaii — it’s only natural that they’d imagine a tropical island would be a haven for that kind of research, and it is. It’s just that the state doesn’t support it. This is an ironic fact:

The Kewalo scientists said that Florida, also an ocean state, has 22 marine labs. “Even Georgia would have more marine labs (four) than Hawaii” if the Kewalo facility goes, said Michael Hadfield, biosciences research center faculty member and former director.

So I should tell my students that Georgia would be a better place to study marine biology? That’s nice for the South, not so nice for Hawaii.

And it’s not as if Kewalo has been unproductive — they’ve turned out some amazing work. Mark Martindale is there, as the director. The man is a Very Big Name in the field of evo-devo — go back through my evo-devo posts, and he keeps popping up everywhere. He’s working on early pattern formation in the metazoans, and his papers are indispensable in understanding early evolutionary events.

An old friend of mine, Elaine Seaver, is also there and doing fabulous work on a promising new system, the polychaete worm Capitella. If you want to know about body plan evolution, we need the kind of comparative approach she’s taking.

Write. Contact:

Gary Ostrander

Vice Chancellor for Research & Graduate Education
Hawaiʻi Hall 211
2500 Campus Road
Honolulu, HI 96822
808-956-7837

Let them know what an incredibly short-sighted decision this is, and what a failure of vision in the making. Not only does it harm the university immediately, damaging their reputation and costing them a useful facility, but think of the message it’s sending, that productive and esteemed faculty at the University of Hawaii can have their work so cavalierly dismissed and their laboratories demolished.

GFP wins Nobel Prize!

The Nobel in Chemistry this year goes to Osamu Shimomura, Martin Chalfie, and Roger Tsien for the discovery of Green Fluorescent Protein, GFP. That’s well deserved — GFP is a wonderful tool, a simple protein that fluoresces. There are lots of fluorescent compounds out there, and most of them require some kind of artificial injection or application to get them into cells — they basically allow you to determine that “a needle was stuck in here“, and also to allow us to visualize the morphology of individual cells, which is all very useful, and there’s quite an industry built around making new probes of this sort. GFP is different. It allows one to use the molecular biology of the cell to generate your green glowing compound. If you want to know when and where a particular gene of interest is expressed, for instance, you just make a construct that couples the regulatory elements of that gene to a GFP gene, and presto, where ever the gene you’re following is turned on, so is GFP, and the cell lights up like a little Christmas tree decoration. That’s powerful stuff: it gives us a tool to follow patterns of gene expression visually, in real time, in living cells.

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Wave those arms in praise of MSKGEELFTG VVPVLVELDG DVNGQKFSVS GEGEGDATYG KLTLNFICTT GKLPVPWPTL VTTFSYGVQC FSRYPDHMKQ HDFFKSAMPE GYVQERTIFY KDDGNYKTRA EVKFEGDTLV NRIELKGIDF KEDGNILGHK MEYNYNSHNV YIMGDKPKNG IKVNFKIRHN IKDGSVQLAD HYQQNTPIGD GPVLLPDNHY LSTQSALSKD PNEKRDHMIL LEFVTAARIT HGMDELYK!

    1 atgagtaaag gagaagaact tttcactgga gtggtcccag ttcttgttga attagatggc 
   61 gatgttaatg ggcaaaaatt ctctgtcagt ggagagggtg aaggtgatgc aacatacgga 
  121 aaacttaccc ttaattttat ttgcactact gggaagctac ctgttccatg gccaacactt 
  181 gtcactactt tctcttatgg tgttcaatgc ttctcaagat acccagatca tatgaaacag 
  241 catgactttt tcaagagtgc catgcccgaa ggttatgtac aggaaagaac tatattttac 
  301 aaagatgacg ggaactacaa gacacgtgct gaagtcaagt ttgaaggtga tacccttgtt 
  361 aatagaatcg agttaaaagg tattgatttt aaagaagatg gaaacattct tggacacaaa 
  421 atggaataca actataactc acataatgta tacatcatgg gagacaaacc aaagaatggc 
  481 atcaaagtta acttcaaaat tagacacaac attaaagatg gaagcgttca attagcagac 
  541 cattatcaac aaaatactcc aattggcgat ggccctgtcc ttttaccaga caaccattac 
  601 ctgtccacac aatctgccct ttccaaagat cccaacgaaa agagagatca catgatcctt 
  661 cttgagtttg taacagctgc taggattaca catggcatgg atgaactata caaa

And the Nobel Prize goes to…

It looks like Alex’s predictions for the Nobel Prise this year did not come to pass — although I was thinking McCulloch and Till were likely, so I was wrong, too. The Nobel for Physiology or Medicine has just been announced, and the winners are Harald zur Hausen, for discovering that HPV causes cervical cancer, and Françoise Barré-Sinoussi and Luc Montagnier for the discovery of HIV. It’s a viral year this time around.

My human lineage

This is a very simple, lucid video of Spencer Wells talking about his work on the Genographic Project, the effort to accumulate lots of individual genetic data to map out where we all came from.

I’ve also submitted a test tube full of cheek epithelial cells to this project, and Lynn Fellman is going to be doing a DNA portrait of me. I had my Y chromosome analyzed just because my paternal ancestry was a bit murky and messy and potentially more surprising, and my mother’s family was many generations of stay-at-home Scandinavian peasantry, so I knew what to expect there. Dad turned out to be not such a great surprise, either. I have the single nucleotide polymorphism M343, which puts me in the R1b haplogroup, which is just the most common Y haplogroup in western Europe. I share a Y chromosome with a great many other fellows from England, France, the Netherlands, etc., which is where the anecdotal family history suggested we were from (family legend has it that the first American Myers in my line was a 17th or 18th century immigrant from the Netherlands). Here’s a map of where the older members of my lineage have been from: Africa (of course!) by way of a long detour through central Asia.

i-9897d9b90311be17c7a9406d91fcf72f-M343.jpg

Hello, many-times-great-grandpa! That’s quite the long walk your family has taken. Howdy, great big extended family! We’ll have to get together sometime and keep in touch.

If you’re interested in finding out what clump of humanity you belong to, it’s easy: you can order a $100 kit, swab out a few cheek cells (just like they do on CSI or Law & Order!), mail it back, and a few weeks later, they send you your results. It’s not very detailed — they only analyze a small number of markers — but it’s enough to get a rough picture of where your branch of the family tree lies. And for a bit more, Lynn can turn it into something lovely for your wall.

By the way, Lynn and I will be talking about the science and art of human genetics in a Cafe Scientifique session in Minneapolis in February.

That’s an old rock

Geologists have just discovered the oldest terrestrial rock yet: some badly battered bit of something called a faux-amphibolite from Northern Quebec, Canada that has been dated to 4.28 billion years ago. I’m afraid most of the paper is way above my head — lots of radioisotope measurements, discussions of the details of the local geology, etc. — but I can at least note that this means Ken Ham is wrong by a factor of over 713,000. I am impressed by both the age of the rocks and the magnitude of the error a creationist can sustain without exploding into a cloud of pink pixie dust that fades to the sound of waning calliope music.

O’Neil J, Carlson RW, Francis D, Stevenson RK (2008) Neodymium-142 Evidence for Hadean Mafic Crust. Science 321(5897):1828-1831.

Reprogramming the pancreas

Blogging on Peer-Reviewed Research

Wow…so have you heard about this result?

One goal of regenerative medicine is to instructively convert adult cells into other cell types for tissue repair and regeneration. Although isolated examples of adult cell reprogramming are known, there is no general understanding of how to turn one cell type into another in a controlled manner. Here, using a strategy of re-expressing key developmental regulators in vivo, we identify a specific combination of three transcription factors (Ngn3 (also known as Neurog3) Pdx1 and Mafa) that reprograms differentiated pancreatic exocrine cells in adult mice into cells that closely resemble β-cells. The induced β-cells are indistinguishable from endogenous islet β-cells in size, shape and ultrastructure. They express genes essential for β-cell function and can ameliorate hyperglycaemia by remodelling local vasculature and secreting insulin. This study provides an example of cellular reprogramming using defined factors in an adult organ and suggests a general paradigm for directing cell reprogramming without reversion to a pluripotent stem cell state.

This is a big deal, I think, so allow me to translate.

First, a little caveat: this is a recent result published in Nature, and it is basic science, not clinical work. Before you start thinking it’s a new treatment for diabetes, I have to dash a little cold water on you and warn you that this has a long, long way to go before it can be applied to humans…but it does open the door to some future strategies that might be applied.

The pancreas is a fairly complicated organ. It’s made up of a variety of different cells that we can toss into a couple of different classes. There are garden variety support cells — mesenchyme, connective tissue, components of the circulatory system, and the ductwork of the organ — that provide building services for the other cell types. Then there are exocrine cells, cells that produce quantities of important substances that are piped directly into the digestive tract via ducts. Among the most important materials exported by this route are bicarbonate buffers to neutralize stomach acids and enzymes like amylase to digest sugars. Finally, the class of cells that most people are familiar with, because they are the subject of a common disease, are the endocrine cells. These are cells that generate hormonal signals that are secreted into the blood stream, and the most familiar of these are the beta (β) cells, which are organized into clumps called islets and which secrete insulin…and if something goes awry with the β cells, the resulting disease is called diabetes.

What the researchers did was identify a small subset of transcription factors, the genes Ngn3, Pdx1 and Mafa, that are sufficient to switch on the insulin production genes in non-insulin-producing cells of the pancreas. They can turn exocrine cells into β cells, which produce insulin, and these cells reduce the effects of diabetes.

The way they did this was to insert the transcription factors (and a gene that makes a glowing protein, GFP, as a marker) into adenoviruses, and then inject the virus directly into the pancreases of genetically immunodeficient (to reduce immune response complications) adult mice. The viruses infected a subset of the pancreatic cells, preferentially the exocrine cells, and started pumping out the transcription factors. As is common in these kinds of genetic engineering experiments, the use of viral transfection is perhaps the scariest part of the story; viruses aren’t trivial to keep in check. However, they report that they also did later PCR tests of adjacent tissues and found no evidence that the virus spread beyond the target organ; they also found that inducing the expression of the 3 transcription factors in other kinds of cells, like muscle, seems to do nothing. These genes are only potent in pancreatic cells that are already primed to be competent to respond to the signals generated by the transcription factors.

The virus is also not needed for long term maintenance of these cells. The virus in the pancreas, as determined by PCR, is cleared away after about 2 months. It seems that all it takes is a brief jolt of expression of Ngn3, Pdx1 and Mafa to switch susceptible cells into the β cell state, and that the developmental program is then self-sustaining.

The authors also made diabetic mice by injecting them with streptozotocin, which kills islet β cells, and then gave them the viral cocktail injection. It did not cure their diabetes, but it did give them significantly greater glucose tolerance, and they did measure increased blood insulin levels. One reason the treatment may not be as effective as it could be is that it simply converts random, scattered exocrine cells into single β cells that are not organized into the islets of the normal pancreas.

A lot of attention has been paid to embryonic stem cell and adult stem cell technologies, and those are both important and provide research and treatment opportunities that must not be neglected, but this is a third way: mastering the developmental control genes of the cell so that we can reprogram mature cells into any cell type we need. While injecting a person’s pancreas with a collection of viruses to rebuild missing cell types might be a little hazardous and crude, there may come a day when we can collect a few cells from an individual by a scraping or biopsy, grow them in a dish to get enough, tickle their transcription factors to cause them to differentiate into the cell, tissue, or organ type we want, and transplant the final, immunocompatible product right back into the patient.

This is the direction developmental medicine can take us — I hope you’re all ready to support it.

Zhou Q, Brown J, Kanarek A, Rajagopa J, Melton DA (2008) In vivo reprogramming of adult pancreatic exocrine cells to β-cells. Nature Aug 27. [Epub ahead of print].