Roger Tsien

Last month, Nobel Prize-winning scientist Roger Tsien passed away.  He helped pioneer the development of Green Fluorescent Protein (GFP) and calcium imaging.  I first heard of Tsien as a first year grad student in my molecular imaging class.  The professors talked about his work so much that my cohort would often joke that the lecture's takeaway was "Roger Tsien is god."

Like almost every biochemist, I used GFP in my own research.  For example, tracing the development of the C. elegans embryo from the one-cell stage through hatching:

from the Murray Lab website, http://www.med.upenn.edu/murraylab/research.shtml

I never met Roger Tsien, but he seems to have been universally respected and liked.  I heard the news of his death almost immediately via Twitter, where many people shared their tributes:

 

What could be less creepy than nested Russian dolls emitting sounds in response to weird hand movements?

For your viewing pleasure:  a video of a bunch of people with Russian dolls containing a musical instrument called the theremin.  This is either really cool or one of the scariest things I've ever seen:

You might know the shrill wailing sound of the theremin from old sci fi films

and the Beach Boys' Good Vibrations.

The theremin is an electronic musical instrument invented by Leon Theremin.  It consists of two antennae that emit and don't receive. The player's hands provide the grounding, and the distance from the hand to the antennae modulates the frequency.

The Russian doll version (the Matryomin) was invented by putting a pitch antennae inside.  I don't think the doll adds anything that another non-conducting receptacle wouldn't, although I guess you can pretend the Russian lady is singing.  Buy your own here.

Better living through ice cream

People always use ice cream to trick others into being interested in science.  Like the famous liquid nitrogen demonstration:

I won't say I'm above such trickery.  I like ad clicks as much as anyone.

Coming to Philadelphia next month is a Thai ice cream shop where a mixture of milk and sugar is frozen to 10 degrees below zero Farenheit on a metal cold plate. Fruit and other toppings are chopped in and then the ice cream is scraped into rolls:

Because of the low temperature, the mixture freezes quickly with small, evenly-dispersed ice crystals leading to a creamier texture, even using milk with lower fat content.

Speaking of low fat ice cream, researchers at the University of Edinburgh, are experimenting with a bacterial protein (BslA) that coats air bubbles and fat droplets and may lead to a more stable ice cream mixture.  The protein self-assembles into a biofilm at both oil-water and air-water interfaces.

The structure of BslA reveals an IgG-type fold with an unusual hydrophobic cap.

For more about the science of ice cream, check out these articles.

I read Mayim Bialik's dissertation so you don't have to: Part 3

Links to Part 1 and Part 2.

Previously:  Mayim Bialik got a PhD in neuroscience for her research into Prader-Willi Syndrome (PWS).

Chapter 2:  Genomic Imprinting in PWS

Summary:  The genetics most people learn about in school is Mendelian.  Mom and Dad each pass on a copy of a gene.  However, genetics is way more complicated than Biology 101 would have you believe.  The genes of one parent can be silenced.  For example, methylation of the mother's DNA changes how tightly they're wound so that the cell machinery can't do it's normal thing with the genes.

In most humans, a portion of the father's genome (the 15qll-ql3 region if you're a genetics enthusiast) would normally be "imprinted" on the offspring.  The father's genes would be expressed and the mother's genes are silenced.

In people with PWS, the father's genes have been deleted.

What do these deleted genes normally do?
Short answer:  We're not sure.

Longer answer:  "MAKOR1N3 codes for a zinc finger motif known to be important for interactions with other molecules (Jong et al., 1999). NDN (necdin) is a nuclear protein that is likely involved in neuronal axon growth and post-mitotic apoptosis (Lee et al., 2005; Pagliardini et al., 2005; Jay et al., 1997; McDonald and Wevrick, 1997). MAGEL2 is a protein that is structurally similar to NDN and may play a role in regulation of the imprinting process and cytoskeletal rearrangements during outgrowth of neurons (Lee et al., 2005; Boccaccio et al., 1999)."

And so forth, etc. etc.  We know what proteins some of the genes code for and what processes they are implicated in, but if you want to know exactly what is happening, that's what science is currently working on.

This is why we need animal models:  Researchers have tried to create mouse models of PWS by knocking out some of the implicated genes to get a mouse with symptoms similar to the disease.  As cruel as animal research is, there is just no way to find out anymore about the disease without them.  The genetics is too complicated to be simulated in cell culture.

Verdict:  Genetics is too complicated.  I think I learned all this stuff in school, but now I have no memory of it.  Also, this seems like a lot of background.  When are we going to get to the research?

Let's talk about the uncanny valley

Because Google reads my email, it knows I am a single woman in my 30s with two cats.  Thus, it keeps showing me creepy eHarmony ads.

Lesson: men with soul patches should date women with possessed eyes.

I find cartoons more and more creepy these days.  I don't know if that's because I don't watch them regularly, so there's the element of surprise when I see Elsa's massive bug eyes and tiny pimple nose.

This slight revulsion to representations of humans that look almost natural but not quite is located in the "uncanny valley," the best explanation of which comes from the episode of 30 Rock where Tracy wants to make a porn video game.

Frank:  Check out this chart.  You see, as artificial representations of humans become more and more realistic, they reach a point where they stop being endearing and become creepy.

Tracy:  Tell it to me in star wars.
Frank:  All right,we like R2D2 and C3PO.

Tracy:  They're nice.

Frank:  And up here we have a real person like Han Solo.
Tracy:  He acts like he doesn't care, but he does.
Frank:  But down here we have a CGI Storm Trooper or Tom Hanks in the polar express.
Tracy:  I'm scared! Get me out of there!        

Frank: That's the problem. You're in the valley now and it's impossible to get out.

I read Mayim Bialik's dissertation so you don't have to: Part 2

Read Part 1 here.

Previously:  Actor and PhD holder Mayim Bialik wrote a thesis on what's going on in the brains of people with Prader-Willi Syndrome.  It's a genetic disease that causes people to eat to the point of obesity.

Chapter 1 - Introduction:

• Bialik's opening sentence is amazing:  "In The Pickwick Papers of 1836, Charles Dickens immortalized a literary character suffering from an insatiable, voracious appetite and the striking ability to fall asleep between bites of food and in the midst of conversation."  What does Dickens have to do with anything?  She speculates the character might be suffering from Prader-Willi Syndrome (PWS).
• PWS is "a neurogenetic disorder with prevalence in the range of 1 in 15,000 to 1 in 30,000 live births." It is caused by a deletion of several genes on paternal chromosome 15.
• Symptoms include" hypogonadism, growth hormone deficiency, mental retardation (with an average IQ of 65... developmental delay, and characteristic facial features: a narrow face, almond shaped eyes, an upturned nose, and a small mouth with a thin upper lip and down- turned corners."
• Best known symptoms include problems with suckling in babies, increased appetite leading to morbid obesity, and compulsive behaviors like skin picking and hoarding.

Three Important Facets of PWS

1. Genetics:  Imprinting is not just something that causes a werewolf to fall in love with the infant daughter of the vampire he previously loved (see Twilight).  Genomic imprinting refers to how genes are expressed differently depending on whether they come from the mother or father's side.  Bialik will cover this further in Chapter 2.
2. Hypothalamic Secretions and Neuroendocrine Function:  "Almost all of the physiological functions subserved by the hypothalamus and pituitary gland are aberrant in PWS."  Bialik will discuss brain circuitry in Chapter 3 and pituitary gland secretions of oxytocin (OT), vasopressin (VP), and cortisol in Chapters 4 and 5.   
3. Behavior:  Beginning at age 3, sufferers of PWS find it harder to feel full after eating, hoard food, and eat unusual flavor combinations.  There are also things like self-injury and aggression and symptoms of OCD.  Further background in Chapter 6.

What is Bialik's research going to do?

Compare hormone levels with how severe their behavioral symptoms are.  She will use blood tests for hormones and written tests for behavior.

Fact:  Genetics does play a role in obesity.  People can't just dismiss that as something fat people say.

Fact:  The word "maladaptive" is going to come up a lot.  It is going to refer to behavior that is commonly described as anti-social or "being a jerk."  (Note - I don't want to be flippant when referring to a disease symptom, but I'm trying to simplify the concepts as much as possible.)

Verdict:  This is one well-written introductory chapter.  Scientists always say to write by telling the reader what you're going to tell them, telling them what you tell them, and then telling them what you just told them.

I read Mayim Bialik's dissertation so you don't have to: Part 1

Mayim Bialik, who you may know as Dr. Amy Farrah Fowler from "The Big Bang Theory" or the titular hat wearer from "Blossom," is one of the most well-known celebrities to have a PhD (real not honorary).  She received the degree in neuroscience from UCLA in 2007.

Many times on this blog, I have mentioned the issue of open access, which means you can't read a lot of scientific papers unless you pay.  I still have yet to write an eloquent, passionate, and intelligent article on the subject, so go here if you want to read more.  Bottom line:  most of you don't have access to Bialik's full thesis, so I am going to read it and summarize here.   I'll go chapter by chapter, but I'm going to start slow with this post.  It's always best to ease into dissertation reading.

Let's get started.

Title:  Hypothalamic regulation in relation to maladaptive, obsessive-compulsive, affiliative, and satiety behaviors in Prader-Willi syndrome  (Translation: what's wrong with the brains of people who have this disease where they eat like crazy)

Acknowledgements:  It sounds like grad school was a real beyotch to Bialik:  "Through an advisor leaving the University, a data set that was contaminated and had to be recollected, an infant who nursed every 2 hours all day for the first year of his life (and continued to nurse every 2 hours all night for the first 2 years of his life); this was the thesis that almost wasn't."  Mad respect to anyone who had a child or children during grad school.  I literally don't know how you did it.  Madder respect to Bialik for use of a semicolon.  And she wins further points for thanking the lab technicians who trained her in addition to the standard professors and fellow students.

Abstract:  Bialik's thesis is going to tell us about abnormal hormone secretions in the hypothalamus (the part of the brain containing the pituitary gland) in people with Prader-Willi Syndrome, a disease where seven genes are deleted or unexpressed and the leading cause of genetic obesity.

Verdict:  I'm very excited to read this dissertation, something I don't think I've ever said, even about the ones my classmates have written.  (Note - I don't think I've read any of their dissertations all the way through.  I'm a terrible friend.)  Bialik comes across as grateful for her educational opportunities while acknowledging how hard the process was.  Her writing is engaging and thoughtful.  She mentions her grandparents "left their war-torn countries of origin as young dreamers--the children of peddlers and tailors--to provide future generations with the opportunity to be free and to live in a place where the streets were paved with gold and you could be anything you wanted to be."  I hadn't heard of Prader-Willi Syndrome before, but I'm always interested in the link between genetics, biology, and behavior.