Pure Biology
apalazzo | October 28, 2009Well this week the University of Toronto hosts the 50th anniversary of the Gairdner Foundation.
If the Nobels are the Oscars of science, and the Lasker Awards the Golden Globes, this event is akin to the 50th anniversary of some big Hollywood studio. There are talks by many of today's hottest science rock stars and many smaller celebrations, which include lunches cocktail parties etc.
This morning we heard from Shinya Yamanaka, probably the hottest rock star scientist of our generation. If you've been asleep for the past few years, Yamanaka's lab discovered how to generate iPS cells from…
apalazzo | October 19, 2009This weekend, I had the opportunity to sit down with a friend, a cancer surgeon who works at a major teaching hospital in the US. He, his wife and two kids were up visiting us for the weekend.
Over coffee, I was asking him about the state of cancer therapeutics. Although he himself does not administer drugs or design treatments, he is part of a larger team which includes molecular oncologists that perform this task. What I heard was quite surprising.
From the vantage point of academia, we have been told that the development of new anti-cancer chemotherapy has been a disaster (here's one…
apalazzo | October 18, 2009Well this year was a big year again for RNA at the Nobels. Both prizes were essentially given to RNA dependent processes. In the case of Telomerase, an RNA molecule, Telomerase RNA (hTR or TERC), acts as the template strand to help Telomerase Reverse Transcriptase (TERT) elongate the end of the telomere. Here's a great vid explaining the whole process:
In the case of the Ribosome - well it is only the granddaddy of all ribozymes. To illustrate this point, here's a great video from the Steitz Lab with an incredible soundtrack:
(HT: Sunil)
Links to essay's on this year's Medicine &…
apalazzo | October 15, 2009
So more than a week has gone by and there has been little press about the science Nobels. And I must say that this year's Medicine and Chemistry prizes are some of the most important in quite a while. But even between the two, the Chemistry is especially important.
Why? I'm not sure. Maybe they were overshadowed by Obama's award??? Or maybe science journalists are sleeping on the job.
I can hear them now "Ribosomes ... boring."
Nothing could be further from the truth.
Ribosomes are arguably the most important biological molecule that we know of. I don't have much time to write long essays…
apalazzo | October 12, 2009Unraveling the ribosome is one of science's Holy Grails. Were God a molecule, he or she would be a ribosome, a veritable galaxy of atoms whose job is to translate genetic code into the stuff of life--protein.
- Brian Maffly, reporter for the Slt Lake Tribune in a recent article, Ramakrishnan: Nobel-winning work started in Utah
(and yes the article features a good friend of mine who worked in Venki's lab)
apalazzo | February 26, 2009Well after a bit of a holiday, the New England RNA Data Club is back. We'll be meeting next week here at HMS. Here's the latest email:
Hello All,
The next meeting of the New England RNA Club will take place Wednesday, March 4th. We will have beverages starting at 5:30PM and talks from 6:00-7:00PM in the Cannon room at Harvard Medical School. Our speakers will be:
Daehyun Baek, Bartel Lab, Whitehead
Lidia Vasilieva, Buratowski Lab, HMS
After the talks we will have food and more beverages. If you are in need of parking, please email us back ASAP. This meeting is sponsored by MERCK, Qiagen and…
apalazzo | February 17, 2009As many of you may know, I have been examining how mRNAs are transported and localized within the cell and how the regulation of mRNA metabolism contributes to gene expression. From data accumulated recently within the "RNA Field", we know that transcription in eukaryotic cells is very sloppy - that is, a plethora of different RNA transcripts are generated from seemingly random pieces of DNA. As I explained in a recent post, some of this background transcription seems to play a role in regulating how the DNA is packed and thus allows for a tighter control of RNA production from protein coding…
apalazzo | December 24, 2008Here I am, in the lab with one last experiment to go before I leave to feast on a Christmas Eve dinner, so while I wait for that last centrifugation step, I'll write a quick post about all these great papers on RNA Polymerase II and chromatin remodelling. As I've said before, if you want to understand what is going on with all of these non-coding RNA transcripts, you have to understand how DNA is organized.
If you don't understand how DNA is packed in the typical eukaryotic (i.e. nucleated) cell, please read this:
How Transcription Affects Genomic Organization and Vice Versa
Then to get you…
apalazzo | December 14, 2008Welcome to the December 14, 2008 edition of the Molecular and Cell Biology Carnival.
Below the fold, we have a great compilation of entries to share with you.
I would like to start off by reminding you that today marks the beginning of the American Society for Cell Biology's annual conference in San Francisco. Although I won't be there, biowrites, the new blog over at the Journal of Cell Biology, will be covering the main events, so check it out.
Next, Charles Daney who blogs at Science and Reason writes about Non-coding RNA and gene expression. The post covers a recent publication by Kouji…
apalazzo | December 11, 2008I just read this fascinating theory that was fully explained in a review that appeared in the latest issue of Cell. This theory connects the origin of cell polarity with aging and it suggests that the centrosome may carry genetic information. Today I'll focus on the first deep connection polarity and aging. Later this week, I'll write about how the centrosome fits in.
What is polarity?
It is the mechanism by which the cell reorganizes its internal structure so that it now has two different sides. These two sides could by "front" and "back" or "up" and "down". So that if you are a crawling…
apalazzo | December 3, 2008First up read yesterday's entry on Genomic Organization.
Now that you've done that, let's talk about a paper that appeared in Nature about a month ago. The article is entitled:
Stepwise chromatin remodelling by a cascade of transcription initiation of non-coding RNAs (link)
Superficially you would look at this title and exclaim Wow another function for non-coding RNAs! Well not exactly. It would seem that everyone is going ga-ga over these non-coding RNAs, but if you dig deeper, something else is going on. Note that I'm not saying that the paper is crap, in fact the results are VERY…
apalazzo | December 3, 2008I just read a paper that features fellow science blogger Chris Patil as an author (although he would be the first to state that he was second on the author's list). The manuscript, which appeared in yesterday's edition of PLoS Biology, describes senescence-associated secretory phenotype (aka SASP), a phenomenon that is associated with cancer cells treated with chemotherapeutic reagents that cause DNA-damage and with cells undergoing senescence. From the paper:
Despite support for the idea that senescence is a beneficial anticancer mechanism, indirect evidence suggests that senescent cells…
apalazzo | December 2, 2008Recently there has been a flood of press about epigenetics and non-coding RNA. What is lacking from these articles is a description of how DNA is packaged and what DNA elements such as promoters and enhancers do. Today I would like to touch upon all of these subjects with a post on how DNA is organized and how this affects the turning on or off of genes.
OK here we go ...
One of the biggest findings over the past couple of years is how the act of transcription feeds back onto the organization of DNA.
What do I mean by that?
Well in our cells, DNA is wrapped around highly conserved…
apalazzo | November 26, 2008The Journal of Cell Biology is one of my usual reads. Recently they've been adding extra features to their site that I really appreciate. A few months back they started a podcast, Biobytes, and now recently they have launched Biosights, a series of on online videos about research published in JCB.
Incidentally the first clip from Biosights is on Allan Hall's latest paper describing how Cdc42, one of the coolest G-proteins in the cell, controls the axis of the mitotic spindle. (Yes Polarity - that same topic that I was telling you about a couple of days back.)
Here is the first eddition of…
apalazzo | November 16, 2008Over the last few years it has become increasing clear that gene expression is partially regulated at the mRNA level.
What do I mean by that?
In eukaryotic cells, the first step of gene expression occurs in the nucleus when regions of DNA are transcribed into RNA. These "transcripts" then encounter RNA binding proteins (RBPs), some which act to process the RNA into a mature message, others that simply bind the mRNA. The whole collection of RNA and its associated proteins is often referred to as the Ribonuclear Particle (RNP). The protein content will dictate whether the RNA is spliced,…
apalazzo | November 13, 2008Traditionally, gene expression patterns were seen as mostly dependent on transcription ... yes those nasty bits of DNA that seemed to be ignored by most "science journalists". But the picture that is emerging is that transcription is looking more and more sloppy, and this "sloppyness" is built into the system so that the act of transcription tends to influence the organization of that part of the genome, regardless of what is being transcribed. It also appears that processes upstream of transcription, (such as mRNA processing, mRNA export and translation) play a greater role in determining…
apalazzo | November 11, 2008If you missed it, today's NY Times Science section has been dedicated to "The Gene" a concept invented 99 years ago by Wilhelm Johanssen.
Overall, the articles were very good, however as a scientist who wants to explain basic concepts of molecular biology to the masses, I have a few problems.
First, there is a misplacement of emphasis on how information flows from DNA to phenotype. The idea that the articles try to convey is that in the old model went along theses lines: DNA contains genes, each is copied into RNAs that are then translated into a certain type of protein ... and then presto…
apalazzo | November 7, 2008There are plenty of large mRNA agregates in cells. In the past few years, two of these structures have gained quite a bit of attention, Stress Granules (SGs) and Processing Bodies (PBs). mRNAs in SGs are loaded with 48S complex, which consists of the small ribosomal subunit, the cap binding complex (aka eiF4F) and the eIF3 complex. SGs are transient structures that are formed in cells experiencing stress such as arsenite, elevated temperatures and amino acid starvation. The key step in forming these structures is the inactivation of eIF2alpha, the protein that carries the initiator tRNA-…
apalazzo | October 27, 2008I have a second to blog - forgive me if it's full of typos (chances are, if you read this blog on a regular basis you're use to them) but it has been a while and I need to get back into the swing of things.
Last week, Jonathan Weissman came over to Harvard Medical School. I had the opportunity not only to hear him talk but also to attend a dinner with Dr Weissman and a handful of fellow postdocs. The Weissman lab has perfected a particular type of science, one that combines high throughput technologies and small reductionalist biology. This approach is the future of biomolecular science.
Let'…
apalazzo | October 20, 2008Last week was a big one for the Rapoport lab.
Throughout my years here, I've come to realy apreciate how structure biology can realy lead to insight. In the latest issue of Nature, two papers describe how proteins are pumped out of cells by the SecA secretory protein.
Background:
You can divide proteins into three classes, those that stay inside the cell, those that are pumped out of the cell and those that must be incorporated into the membrane. The problem with the last two classes of proteins is that they must cross a membrane. This is accomplished by the translocon, a protein conducting…