News from lab

There's some good news coming from lab. For my January science update, I'm happy to fill you in on the big publication that just came from my boss Keisuke. On January 6, the journal Neuron published his latest findings in an article entitled "Congenital Nystagmus Gene FRMD7 Is Necessary for Establishing a Neuronal Circuit Asymmetry for Direction Selectivity." Quite a mouthful. So let's break this down.

"Congenital Nystagmus Gene FRMD7 Is Necessary for Establishing a Neuronal Circuit Asymmetry for Direction Selectivity"

1. What is congenital nystagmus?
This is an inherited visual disease which occurs in approximately 1 in 1500 individuals. The symptoms of the disease include a lack of optokinetic reflex, the reflex which allows to focus on objects in a moving field, and spontaneous involuntary horizontal eye oscillations. This video does a great job illustrating the condition.

Patients with this condition have severely impaired vision and can have serious social challenges stemming from the aesthetics of the condition. The severity of congenital nystagmus varies from patient to patient, and we don't quite understand why. More importantly, we don't know what causes it, and certainly not how to treat it. (*There is one technique for eliminating the spontaneous eye movements which involves cutting and re-attaching the eye muscles, and even so, we don't know why this works.)

"Congenital Nystagmus Gene FRMD7 Is Necessary for Establishing a Neuronal Circuit Asymmetry for Direction Selectivity"

2. What is FRMD7?
FRMD7 is a gene expressed in limited areas around the body, most especially in certain retinal neurons. It interacts with a membrane-associated protein, and it is especially important during development, but its activity isn't really understood. Several genetic studies have quite clearly linked mutations in this somewhat mysterious FRMD7 gene to congenital nystagmus in humans. How these mutations were causing this condition were totally unknown, until now.

"Congenital Nystagmus Gene FRMD7 Is Necessary for Establishing a Neuronal Circuit Asymmetry for Direction Selectivity"

3. What is neuronal circuit asymmetry? And why does it matter for direction selectivity?
First, let's take a look at something called direction selectivity. This refers to the ability of certain neurons in the retina to respond selectively to the movement of objects in a certain cardinal direction: up, down, left, or right. This ability of different neurons to respond to motion in one of the four directions is what allows us to detect moving objects. These neurons develop their direction selectivity after the brain tissue has significantly developed. In mice, it happens after birth, just a few days before they open their eyes. In humans, we assume that the development is similar, though we don't know for sure.

The direction selectivity is established through "circuit asymmetry," the formation of asymmetric circuit connectivity between starburst cells and their downstream signaling partners, the direction-selective (ganglion) cells. The starburst cells are a set of cells which respond more strongly when the light signal begins at their cell body and then moves out into their dendrites. (For instance, if an image signal moves from left to right across this cell, it won't elicit much of a signal from the dendrites on the left of the cell body, but it'll elicit a big signal from the dendrites to the right of body, which it passes after passing the cell body.)

A generic picture of a starburst cell which I grabbed from Psychology Today. The big spot in the center is the cell body, from which all the dendrites emanate.

These starburst cells form stronger connections with the direction-selective cells whose directional preference aligns with the preferences of the starburst cell's dendrites. We don't really know how the starburst cells know how to pick and choose the cells whose preferences align with their dendrites, but we know that they unevenly pair-up with direction-selective cells, at least in healthy individuals...

And here comes Keisuke's contribution: his original work, which just got published in Neuron, shows that mice with a mutated FRMD7 have problems with their direction-selective circuits. Specifically, their up and down direction-selective cells are just fine, but the left and right ones, the ones you'd need to focus on a horizontally-moving object and to keep your eyes from spontaneously oscillating, are all but non-existent in mice with this mutation. And remember, we know that humans with this mutation have congenital nystagmus: they can't focus on objects in a horizontally-moving scene, and their eyes oscillate horizontally. It looks like, in this case, the mouse is probably a pretty good animal model for this life-altering human disease. Through studying this mouse, we think we have the first major breakthrough in understanding this hitherto mysterious human disease.

If our extrapolations from mice to humans are correct, as they seem likely to be, then we now understand that humans with congenital nystagmus are lacking horizontal direction-selective circuits in their retina. This is a major step in understanding the neuronal circuits underlying this disease, an important step towards being able to develop a medical treatment. And more broadly, this is an important step in linking genetic mutations to problems in neuronal circuits. As Keisuke is quoted as saying in a popular science summary of his publication, "To my knowledge this is the first time that we can link a disease to a defect in neurocomputation."

I hope this was clear, and that it gives you a good idea of what that lab and I are working on.

It will be exciting to see where our investigations into the circuitry defects of congenital nystagmus will go over the next few years. Stay tuned!

A new year, a new look

Happy new year from snowy Aarhus!

After a couple of weeks back stateside, exchanging presents, testing apple cider mimosas, and camping out with cousins,

Family Christmas 2015 (including the family trip to the Franklin Institute)

having survived a bus trip up to frosty Toronto to catch up with friends and family,

Toronto, until we meet again

and even squeezing in a day-trip through the Big Apple,

There's nothing quite like Rockefeller Center and the windows at Saks Fifth Avenue at Christmastime.

I've dived back into the Scandinavian winter, which is finally more wintery this side of the new year.

Mars couldn't quite decide if today's snowflakes needed chasing or were fierce enemies to run from.

And in keeping with the fresh starts that come along with the new year, I'm going to be striving for something new when it comes to this blog. For now I'm thinking of rotating weekly updates on my four favorite themes: science, pole dance, Aarhus, and travel. I'm not sure yet just how I'll spin it, but keep an eye out.

Our first Christmas in Aarhus

As Christmas seasons are wont to do, this year's in Aarhus flew by. Being our first in Denmark, it was filled with cultural discoveries, from the charming to the somewhat disappointing. To lay it out there, the Danes aren't big on lavish holiday displays. Unlike New York or Paris, Aarhus doesn't light up for the holidays. Beyond a few major shopping streets and the mall, the streets were as dark as ever, which is saying something given the amount of daylight this far north at this time of year.

It felt like I scoured the entire city to find this much outward expression of holiday cheer. Showy is one word you can't put on the Danes.

The Christmas markets also weren't something to write home about. If it hadn't been for the mulled wine, "gløgg," which the Danes have really mastered, I'd have been hard-pressed to find much to tempt me past the first couple of disappointments. France spoiled me, in more ways than one. But then again, there were the æbleskriver, the puffy bite-sized pancake balls that the Danes dip in powdered sugar and jam around the holidays. I guess there were a couple things to keep me coming back.

The Christmas markets aren't all they're cracked up to be in Aarhus.

Luckily, you can forget about the Christmas markets over a gløgg and some æbleskriver.

All this is hardly to say that the Danes don't do Christmas. Far from it. The entire month leading up to the holiday is filled with Christmas parties for offices, departments, clubs, teams, and friends. These epic all-night parties (which is saying something, since the sun sets before 4pm and doesn't rise until nearly 9am) are called the Julefrokost, or Christmas lunch, though I still haven't figured out why they call an evening event a lunch. Perhaps it's just typical Danish modesty, as calling it a dinner might sound haughty. Who knows? Regardless, the julefrokost does include a large sit-down meal loaded with all sorts of typical Danish foods: liver paté, lots of red cabbage, "sweet potatoes" (literally potatoes coated in caramelized sugar), duck, and the classic Christmas rice pudding with whipped cream, almond slivers, and cherry compote, the risalamand. Lurking in the depths of the risalamand is a whole almond, whose discoverer is rewarded with prizes like sweets or small gifts. The trouble with trying to slip in a whole almond in a dish packed with almond slivers is that finding the fugitive isn't always so easy. Mix in a few shots of schnapps and the whole almond can go down all too easily, leaving everyone's stomachs packed with the rice pudding— it absolutely had to be searched— and the prize unclaimed, as happened with us this year. (A subsequent dance-off seemed the only logical way to resolve the issue of who should take home the prize.)

Mmm, risalamand. (Prize not included.)

One of my favorite touches of a Danish Christmas is their advent calendar. It's got to be one of the most simple yet charming interpretations I've seen so far. Very fitting for the Danes in their constant quest for hygge, or cozy charm.

Nearly done counting down the days!

And with all that, it's time for me to call it a night. From the Billund airport, where I await my absurdly early Christmas Eve flight home, I'd like to wish you a very merry Christmas.

A Danish Expat Thanksgiving

The Danes may do the Fourth of July, and they've even imported Black Friday, but Thanksgiving has yet to cross the pond. And so I was pleased to induct a large group of newbies into my favorite American holiday this weekend. This year's grand challenge was the turkey, a responsibility I'd managed to hand off every year since I'd begun finding the bird in Paris. There was simply no more dodging the bullet. Luckily, my househusband*'s master culinary skills (I think the French are just born with it), finely honed over the past few months, came to the rescue. Wrapped in aluminum and stuffed with herbs and lemon for flavoring, our turkey came out surprisingly moist and flavorful. (*Nicolas is at home now while in professional transition and I'm affectionately calling him my househusband. You haven't missed out on any surprise wedding.)

A Thanksgiving turkey success thanks to Nicolas

Allrecipes.com was our best friend this weekend. Besides the turkey, we tested out a collection of recipes: gravy with a hint of tomato paste, buttermilk cornbread (with wholewheat flour), a "Thanksgiving turkey" bourbon citrus cocktail, sweet potato casserole, pumpkin pie cheesecake, and a traditional American hot buttered rum. Coupled with our friends' salads, curry, cheesy bread snacks, mashed potatoes, brownies, and sugar pie, we had ourselves a proper feast.

Our Thanksgiving feast

Our guests hailed from places as diverse as Germany, Denmark, France, Hungary, Ireland, Canada, Honduras, the Faroe Islands, and (if you want to count country of origin) even Bosnia and Iraq. By comparison, Nicolas was a seasoned veteran clocking in his second Thanksgiving. In all, it was a real melting pot of a Thanksgiving which, in a sense, couldn't have been more American, in spite of the total lack of American guests. It didn't take much arm-twisting to convince our foreign friends that the Americans have a few good ideas when it comes to this celebration.

The Thanksgiving bouquet brightened up our windowsill to bring some extra holiday cheer.

All in all, it was a wonderful Turkey Day.

Postdoc update: Finding beauty in the (very) little things

With the click of a button today, I submitted my final funding application for the fall 2015 season. It's been a rude, if unsurprising, wake-up call to what it means to be a postdoc-- so many long hours staring at screens, reworking paragraphs, and looking for just the right turn of phrase that might convince someone that my science is just the thing that will lead to that next great break-through, all the while wondering if that's even close to the truth.

I'd love to be able to share more about my project, but my hands are tied. Such is the depressing reality of science these days: it's all so cut-throat that nothing can really be shared before it's all wrapped neatly in a bow and published. Broadly, I am looking to better understand how the circuits develop in the eye (the retina) that allow us to detect motion. We've got some genes that we're particularly interested in, and some implications for better understanding the visual disease called nystagmus. I'm also working to develop tools that fall under the broad category of "optogenetics," a hot new field in science in which we design genetic systems which allow us to use light to control, manipulate, and record from neurons.

What I'm lacking in specifics, I thought I'd make up for in a little art gallery of recent scientific images. The first two are from a series I affectionately call my Starry Night collection.

Starry Night 1/2

Starry Night 2/2

These images are taken from plates of cultured cells growing densely together. I was shocked to find such beauty pop up under the microscope!

This next image is more meaningful. I call it Visualizing Vision. This is a highly magnified image of a cultured mouse retina, which closely resembles that of a human. In it, you can see a whole lot of blue amacrine cells, little intermediate cells in the chain of retinal information flow, which begins with the light-sensitive photoreceptors and goes all the way down to the ganglion cells, which form the optic nerve that sends preliminarily processed visual information along to the brain, in the form of a handful of parallel channels that each carry different aspects of the visual scene. In pink, you can see two ganglion cells, both reaching out to the hole in the top left, from which the optic nerve used to exit the retina and travel to the mouse's brain. In those pink cells, we can see axons extending toward the brain, stretching their fingers in an easily visualized goal of passing along the message as it is begins its transformation from little photons of light into that complex sensation we know as vision.

Visualizing Vision

I might be a burned-out researcher, and a postdoc filled with doubts about my future. And yet, sometimes I see images that really make me pause in amazement. I might read a thousand different charts and diagrams and textbook explanations of how the retina works, but there's just nothing quite like holding one in my hands, placing it under a microscope, and seeing its beautiful functional design first hand, knowing that I am looking at the very system that allows me to look, to perceive the visual world. I hope I was able to transmit a little bit of that wonder to you today.

A snowy championship weekend

If you know me or you follow this blog, you've probably realized that pole dancing is not just restricted to night clubs, but it also a sport. And, where first comes sport, next comes championships. And that's what happened in Denmark (and not for the first time) this past weekend.

My friends and I ventured down to what the Jutlanders call "Sweden" (a proper Danish insult), and what the rest of us would call Denmark's capital city. And, from our front row vantage point, the competition was way more exciting than YouTube. Still, it's worth a share. The highlight of the night was the guy who literally backflipped off the pole. None of us had ever seen anything like it.

Bjarke Hellden Pole DM 2015

And of course, our own lovely instructor put on quite the performance too! Another girl in our studio took second overall. It's worth checking out if you've never seen a pole choreography before.

By the time the excitement was over, we emerged from the theater to discover that the light dusting that had begun outside had sped past "charming": there would be no getting home that night.

Snowed in at the Danish pole championships

But a snowed in camp-out in Copenhagen with your pole girls isn't the worst way to spend a Saturday night. And after all that fun, I got to come home to this guy discovering the cold white stuff.

An extra weekend highlight: Mars learned about snow.

Another Copenhagen Chi Connection

Chi Connection: what we sorority girls call it when Alpha Chi's got together, preferably somewhere faraway and exciting, and certainly outside of the confines of campus life.

Another AXO reunion in Copenhagen!

It's been a few years since I've left my dear old alma mater, but it hasn't stopped the most welcome visits to my corner of the world from some of my lovely sisters. Back in August, I was thrilled to cross paths with Amy when her Euro-travels and my summer training course brought us both to Copenhagen. This time, in our first reunion since we'd both been French residents, I finally had a chance to catch up with Minh!

Nyhavn in November: we won't be seeing much sun in these parts until next spring

Our weekend together was standard Copenhagen: wandering along the canals, through the park-like Assistens Cemetery, around the 17th century military fortress Kastellet, past the Rosenborg Castle, and of course down to Mikkeller & Friends for some Danish craft beer. There was good food, great company, and wonderfully delicious Danish cuisine. We even discovered that the Danes serve their take on mulled wine, gløgg, complete with sliced almonds and raisins that puff up plump with spiced wine. Another check in the plus column for Danish cuisine and for tourism in their capital city.

Gløgg: Danish mulled wine. At Cafe Gavlen. Delicious.