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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.

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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:

(Original video removed)

UPDATE APRIL 2015: The above referenced paper and two related papers by the same authors were recently retracted. Cell’s notice contains the most detailed description of the problem.

Retraction notices:

http://genesdev.cshlp.org/content/29/6/686.1.full

http://genesdev.cshlp.org/content/29/6/686.2.full

http://www.cell.com/cell/fulltext/S0092-8674(15)00367-0

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.

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