You'd Prefer An Argonaute

More evidence of non-boring scientists

Posted in Media, MIT by YPAA on December 17, 2011

Dennis is a cool dude; it’s self-reinforcing in his staff.

Remember, no grant could ever fund this kind of lab environment!

Kim Lab, Department of Biology, MIT

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R.I.P., H. Gobind Khorana

Posted in Media, MIT by YPAA on November 14, 2011

FalconCAST

Posted in Gallimaufry, Lab Life, Media, MIT by YPAA on May 18, 2011

More than a year ago a pair of Peregrine Falcons made their new home on the roof of our institute. They endeared us with their swooping through the air, their calling and playing, and their leaving various rodent body parts on outside windowsills. So cute!

This spring some furry chicks emerged, and now one can watch the whole family on a live webcam, FalconCAST. It’s a way to kill that time during your 4 degree spin. See the chicks roost, feed, and projectile poop.

Update 6/15/11

Man, they grew up fast. The following message was posted on our internal site this morning:

The falcons that hatched on Whitehead’s 7th floor have fledged and left their nest. Two of the falcons flew off earlier last week, and the last one departed on Saturday, June 11th. The parents will continue to feed the fledglings as the young learn the finer points of flying and mid-air hunting. Because the nest is no longer occupied, the FalconCast has been turned off.

Update 2012

The falcons and FalconCast are back online with hi-res camera.

Evidence of non-boring scientists

Posted in Lab Life, MIT by YPAA on February 17, 2011

One of the most clever lab homepages I’ve seen:

Kim Lab, Department of Biology, MIT

Things like this instantly raise the coolness factor of a lab.

Bonus: they do schweet research.

Scott Valastyan teaches the AACR about microRNAs

Posted in Conferences, MIT by YPAA on April 23, 2010

My homie Scott; his audience continues to expand…

Honey Bee Genetics

Posted in Blog Affairs, Gallimaufry, MIT by YPAA on November 19, 2009

The posts have been slow to rise lately, because I’ve been busy with things:

  • I’m writing a paper.
  • I’m still taking that Science Journalism course, and working on a final ~3,000 word piece, which I’ll put up–here or elsewhere–when I’m done. I can tell you it’s about some brilliant research coming from the lab of Dianne Newman, an MIT Professor.
  • As usual, I’m banging drums in an MIT jazz combo. This term we’re playing, among others, the James Brown song “Mother Popcorn,” and it’s sooo funky.
  • Other miscellaneous debris.

To tide readers over until a more steady stream of original content appears, I am posting something I wrote three years ago, when I was a wet behind the ears first year graduate student. The Department of Biology has a wonderful class, only for the first year grad students, called “Methods and Logic in Molecular Biology” (colloquially known as “seven-fifty” or “Methods”), an intense paper reading course led by several faculty. (Actually, eventually I should probably write some posts about these classes for potential students or others who are interested?)

Anyhow, our section for Methods became somewhat tight, and occasionally we exchanged emails about the current week’s assigned papers. Around 2am on the day of the last class of the semester, I sent the following email to my section. Clearly I was high on something–not a controlled substance; possibly a couple beers; likely joy at almost being done with the class/semester; as likely rebellion against being told what to read, instead choosing to read what I wanted to. Most of my classmates had already exhibited in spades dysfunctional behavior, it was my turn. I still think it’s a stimulating read:

On the eve of our last class, instead of re-reading the papers I did some Internet research into the fascinating area of honeybee genetics. Topic is more interesting than heat maps or MALDI experiments. Some things I found:

In a bee colony, there are three types of bees: few female queens, hundreds of male drones, and thousands of female workers. Females are diploid and males are haploid. Females develop from fertilized eggs. Haploid male drones develop from unfertilized eggs, and therefore they have no father! Sex determination is made at a single locus, the csd gene, of which at least 19 alleles are known. It seems that all alleles can be found in males and females. It was also shown that once activated, csd remains active throughout development. RNAi inactivation of csd causes diploid female eggs to develop male gonads, but does not affect haploid male egg sexual development. Therefore it has been hypothesized that 2 different alleles of csd somehow result in two protein products that can interact together to direct a specific step in the sex determination pathway towards female development. Hemizygous csd eggs cannot make this product, and thus the default state is male.

Female queen and worker bees develop from queen bee eggs fertilized by drone sperm. Females must be heterozygotes for csd alleles to survive. Diploid flies homozygous for a csd allele develop into sterile males, but soon after these larvae hatch from the comb, they are selectively removed and destroyed by worker bees (not sure how workers can recognize these larvae). (This also makes it difficult to develop inbreed stocks of honey bees, colonies die out quickly due to loss of csd homozygotes.) Since both queens and worker females come from fertilized eggs, what distinguishes them is that between larvae and pupa stages, queens receive a hormonal mixture called the “royal jelly”, whereas workers arise from larvae that have been denied this. Workers are sterile because they don’t develop ovarioles, and only live a few weeks. Queens usually mate once in their life and then live for years.

Queen bees must mate with many drones at one time early in there lifetime, and must do it 50-100 meters in the air and kilometers from their colony! (This makes it difficult for bee breeders to maintain isogenic stocks of bees, an intensely studied research problem in bee genetics.) The drones die after mating, and the queen returns to hive and doesn’t need to mate again. She will produce thousands of offspring from eggs fertilized from perhaps 5-15 drones. From an evolutionary perspective, the fact that she usually mates with multiple partners once early in life, and far from the hive prevents her mating with her own son, reducing the chances of producing half inviable progeny homozygous for csd allele, (which means fewer worker bees to support the colony). Pretty cool, huh.

Oh yeah, consider this my contribution to Thursday’s discussion.

Sorry, but I can’t remember my references.

Venki Ramakrishnan: the Cadillac of ribosome structure investigators

Posted in MIT, Talks by YPAA on October 28, 2009

ramakrishnan

Give this man a Nobel Prize. Give it to him.

I know before I’ve made clear my affection for Harry Noller, and that affection still remains strong like a peptide bond, but lately I’m head over heels (head over sneakers) for Venki Ramakrishnan. Last week in his lecture for the MIT Biology Colloquium, Venki Ramakrishnan charmed me and several hundred other people with his humor, smarts, and beautiful structural work.

The scene of Venki’s lecture, titled “How the ribosome facilitates selection of the right tRNA during decoding of the message,” was quite a spectacle. There was an electricity in the air. Never had I seen room 32-123 so packed. Every seat was taken, of course, and there were at least one-hundred other people huddled in the back of the lecture hall, down the stair aisles, in front, everywhere. Some professors were seated on the concrete floor.

Venki’s faculty host had warned the audience before the lecture began that the aisles had to be clear (for fire safety reasons), and so they were cleared. But sure enough, ~10 minutes into Venki’s lecture, the honorable MIT campus police unkindly entered the room and, temporarily, ruined some beautiful science.

It was quite funny: Venki was captivating us from the lectern, as he faced a projection screen to his left. To his right, a plump MIT police officer sauntered in, unbeknownest to Venki, but knownest to everyone else in the room. The copper reached his arm out to the lectern to capture Venki’s attention, Venki stopped talking, and the officer motioned to follow him outside the lecture hall. Totally perplexed, Venki obliged and left the room, to a chorus of boo’s directed at the police. Moments later, Venki emerged calm as a clam, and succinctly directed movement of his audience into a fire-escape safe arrangement so that his lecture could continue.

Imagine what Venki’s story could sound like: “I won the Nobel Prize, went to MIT, and was accosted by the campus police at my own lecture!”

Venki gave a beautiful introduction, even making a jab at Jim Watson (Watson the man, not Watson the scientist). (He also later hilariously and appropriately mocked Tom Steitz.) He then proceeded to give the best structural biology talk I have ever seen.

He described how proper base pairing between the tRNA anticodon to the mRNA codon induces subtle structural movements between that end of the tRNA and small subunit RNA that are transmitted up through the tRNA toward its aminoacyl end, inducing residue movement in EF-Tu leading to GTP hydrolysis–a cascade of events leading to EF-Tu release and aa-tRNA incorporation. (For more, see Venki’s recent review.)

He ended by narrating an incredibly cool animated movie of all the ribosome structural movements he had just described in detail, and then reprised the movie with a version set to a soundtrack of snippets of classic pop tunes (e.g. by The Clash, David Bowie, etc.), arranged by his lab. The lyrics spoke to the molecular movements spotlighted in the movie. It was very entertaining.

I realize I could have proclaimed Venki the “Rolls-Royce” of ribosome investigators, since he’s at the MRC. But no. He’s American; he’s a Caddy.

Evolution in a Test Tube

Posted in MIT, Science Journalism by YPAA on October 8, 2009

David Bartel’s career as a biochemist began marked by tension between his exceedingly meticulous method and the most careless of biological processes. Evolution, the process in which living things change and diversify from their predecessors, is random, at moments appears illogical, and leads to many dead ends. But in a seminal paper published in 1993, with clear thought and clever technique Bartel, along with thesis advisor Jack Szostak, brilliantly distilled the highly complex nature of evolution literally into a test tube.

Bartel focused on “ribozymes,” a class of molecules composed entirely of ribonucleic acid (RNA) that catalyze chemical reactions. Starting from a synthetic large pool of different RNA molecules of random sequence, he used a technique called in vitro selection to isolate a new type of ribozyme that performed a specific chemical reaction, known as an RNA ligation, otherwise only attributed to natural protein based enzymes. He then evolved these ribozymes by introducing random mutations into their sequence and re-isolating more active versions that outcompeted earlier variants—in effect modeling evolution in a test tube.

Naturally occurring ribozymes are rare—a host of enzymatic activities they may have once possessed have been appropriated to faster and more accurate proteins during evolution—but owing to their structural similarity to DNA, and catalytic potential, they are attractive candidates for the original self-replicating macromolecules, predating more complex life forms.

While generation of a self-replicating ribozyme remains elusive, and would not prove that catalytic RNAs directly preceded life, Bartel’s study was paramount in demonstrating the ability to isolate ribozymes with new activities. He notes, “We’re left with lots of gaps in knowing how RNA based life forms might have emerged, but it is still useful to know what RNA can do.”

Appreciating the highly mutable nature of evolution, Bartel also recognizes that the particular ribozyme he isolated was only one possible outcome of the experiment. “Evolution is the sum of a huge number of chance events, and the biological world is the culmination of all these chance happenings,” says Bartel. “If you replayed a tape of biological evolution, we would all look different.”

Reference: Bartel and Szostak, Science 261, 1993.

I wrote the piece above for another assignment for my science journalism class. The assignment was a “front of the book” magazine piece, written for an audience interested in science, but probably not very knowledgeable about RNA or ribozymes.

We were instructed to pick a paper we are (were, have been, etc.) excited about, and interview one of the authors or an expert in the field. Ribozymes are what first sparked my interest in RNA back in college, so I picked my favorite ribozyme paper. And conveniently, being at MIT, I had the opportunity to interview Professor David Bartel, the first author of the paper.

What are microRNAs?

Posted in MIT, Science Journalism by YPAA on September 29, 2009

MicroRNAs (miRNAs) are tiny molecules composed of ribonucleic acid (RNA) that modulate the expression of genes. In nearly all known cases, these tiny RNAs reduce the level of protein produced by their gene targets.

To accomplish this task, miRNAs chemically pair with messenger RNAs (mRNAs), the molecular intermediates between a gene’s DNA sequence and its protein product. This pairing event essentially sequesters the mRNA, preventing it from being decoded to produce protein.

Recognition of an mRNA by a miRNA is imparted by complementary molecular motifs present in both molecules. These molecular motifs are encoded in the DNA sequence of a genome.

MicroRNAs compose a class of gene regulatory molecules widespread and evolutionarily conserved throughout plants and animals. While miRNAs’ effects on gene expression are modest compared to other modes of gene regulation, en masse their total contribution to gene expression in the cell is significant.

The ~150 word definition of microRNA above I wrote for an assignment in a science journalism class I am taking this semester. (Incidently, you may have noticed the frequency of my contributions to this blog has slowed in recent weeks, resulting from an increased non-blog workload. Sorry.)

The assignment was to write an “explainer” for a key scientific term, like you might see set aside from a longer article (in a Scientific American or Discover type magazine) concerning some scientific idea, that references the term. Thus it is meant for a audience interested in science, but not necessarily familiar with the scientific details of whatever topic is under discussion.

My class had mixed reaction to my explainer. The paragraphs were deemed somewhat disconnected in content from each other, perhaps resembling more of a list of facts in the form of sentences. Some found the voice dry and boring (like that of a scientist’s?).

My goal in writing it was to define microRNAs: (1) What they are; (2) What they do; (3) How they function; (4) Why they are important. I could have started with the importance, but the way I wrote it is the way my brain organizes thoughts. I should learn to think like my reader, and also make the language a little more, um, charming.

Scott Valastyan teaches Bob Weinberg about microRNAs

Posted in Media, MIT by YPAA on June 14, 2009

Led by the sage Scott Valastyan, a graduate student in Bob Weinberg’s laboratory, a new study in the June 12 issue of Cell demonstrates miR-31′s role in inhibiting breast cancer metastasis. Cell’s website recognizes the paper with a video where Bob and Scott are a first-rate scientific tag team:

Bob Weinberg’s Words of Wisdom

Posted in MIT, Talks by YPAA on May 22, 2009

A few days ago I attended an informal talk by the cancer biologist Bob Weinberg, who discussed some of his family history, upbringing, and early career, peppering many chunks of wisdom onto the attentive audience throughout. While introducing him, a colleague mentioned that Bob has received 62 awards for his scientific pursuits. Among these are the National Medal of Science (1997), and the Wolf Prize in Medicine (2004). He has also written the reference textbook on cancer, The Biology of Cancer. So as a scientist and educator, this man is solid gold.

Weinberg recounted one story about how, in the early 70′s, he crossed paths with a fraud who had shared his intense interest in the mechanisms by which infection with DNA tumor viruses could lead to transformation of mammalian cells. Weinberg had thought of several experiments to address the question, only to find out soon after that another investigator in Toronto had beat him to it, becoming a minor celebrity while giving talks up and down the east coast. However, the unthinkable quantity of data this investigator had amassed would soon end his career. (This outcome is assumed as Bob did not provide a name.) The data was fabricated. The first hint resulted from a back of the envelope calculation by a journal editor showing that the number of petri dishes required to generate the data far exceeded the number available to all scientists in the Toronto area during the relevant period.

Hot fields are of course vulnerable to fraud. Recently there was Woo Suk Hwang in the stem cell field, and Luk Van Parijs ran a lab studying RNAi technologies and immunology. Back in the late 80′s/early 90′s there was the notorious Imanishi-Kari/Baltimore affair. I suppose it’s possible that immunology was hot back then. Stranger things happened.

So how ’bout the small RNA field? No big scandals I can recall, (although I’m fairly new to the field). A search for the terms “miRNA” and “retraction” in Pubmed yields 3 results: one Science paper and a couple Nature papers. However, retracted papers and scientific fraud are not one and the same.

The controversies in the small RNA field seem to encompass smaller battles, say a partially disputed and highly visible paper with data that is not totally rebuked by others, but where the authors make overly great leaps in their interpretations. And as a colleague of mine pointed out, the field is so new and moves so quickly that there hasn’t been enough time for researchers to confirm all previously published results.

A paper claiming miRNAs can up-regulate translation under certain cellular conditions generated a lot of controversy. A recent presentation of this work by Joan Steitz at the Keystone meeting in April, more than a year after its initial publication, was still met with some underlying skepticism in the questions that were asked.

Bob Weinberg himself published a miRNA paper that generated some discussion in journals (1), and at conferences (2). But these last two examples are really cases of a healthy scientific discourse, openly discussing results and interpretations.

While in the literature I regularly encounter dubious data, it’s more often the dubiousness of some of the interpretations that bothers me. For novel published data I think it is beneficial to temper skepticism with belief. Considering alternative explanations for what one may consider questionable data is a much better intellectual exercise than discounting an entire paper, and just ragging on it.

But hey, what do I know. Listen to a guy like Bob Weinberg. He said he doesn’t even read the literature. He just talks to people.

(1) http://www.nature.com/nature/journal/v455/n7216/full/nature07362.html; http://www.nature.com/nature/journal/v455/n7216/full/nature07363.html

(2) Witnessed at Keystone RNAi, MicroRNA, and Non-Coding RNA 2008 meeting

MIT Faculty Open Access Policy FAQ

Posted in MIT, Open Access by YPAA on April 13, 2009

Ironically I ran into this through Peter Suber’s OA News blog, here. The policy is sourced from MIT Libraries OA site, where a shortened version viewable to the public can be found. Below is the whole enchilada. Feast on it:

MIT Faculty Open Access Policy FAQ

PURPOSE AND AIM OF THE POLICY

Why are we doing this?

In the eyes of many faculty, the goal of disseminating research is best served by using the unified action of the faculty to enable individual faculty to distribute their scholarly writings freely.

This view of the importance of open access to the faculty’s writings is especially apposite in the face of increasing efforts by some commercial publishers to further close access to the scholarly literature they control. Other organizations with a vested interest in scholarship are independently supporting such efforts as well. For instance, the Wellcome Trust requires any scholarly articles on research they fund to be made openly accessible. The National Institutes of Health, by congressional legislation, have recently instituted a similar requirement, mandating posting in the open-access PubMed Central repository.

Isn’t this unprecedented?

No. Harvard University’s Faculty of Arts and Sciences and Harvard Law School, as well as Stanford School of Education, have similar policies. As mentioned above, the Wellcome Trust mandates an open access requirement for their grantees. NIH also has a policy mandating open access.

What’s in it for me?

The Internet and web have enabled individual faculty to make their articles widely, openly, and freely available. Research has repeatedly shown that articles available freely online are more often cited and have greater impact than those not freely available, and this trend is increasing over time. Consequently, many faculty already make their writings available on their web pages, sometimes in potential violation of copyright law and sometimes through individual copyright negotiations with publishers. This policy will allow you to make your writings openly accessible, and it will enable MIT to help you do so.

(more…)

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