Pure Biology
apalazzo | February 21, 2008Fundamentaly biology is about information. An evolving entity must be able to copy itself - it needs the information on how to make a copying machine and it needs to copy this information to its progenitors. Already you can see how this works.
INFORMATION => COPYING MACHINE => COPY INFORMATION
Of course it is much more complicated then that. Take step A (INFO => COPY MACHINE) how do you do that? Well there are other machines that will translate the INFO into MACHINE parts. This process lies at the core of biology, the transfer of information, which is stored in DNA and is coded by…
apalazzo | February 9, 2008I'm almost done with my grant. Yesterday I sent out a 95% completed version of my proposal to SPA (Sponsored Programs Administration - an organization that vets grants to make sure that there are no conflicts of interests and that all the proposed protocols treat human and vertebrate animals ethically - since my research uses tissue culture cells, this ain't a problem). Next I had to take care of all the other items I had been neglecting. Priority number two was the RNA Club. Here is the letter I sent out:
Hello All,
The next meeting of the New England RNA Club will take place Thursday,…
apalazzo | January 16, 2008Well a study just came out that there are lots of little non-coding RNAs expressed in interesting patterns in the Brain. I've actaully heard about similar unpublished data from some other sources.
Does this mean that the genome is filled with functional ncRNA encoding genes? Hold your horses. As noted elsewhere, these little bits of RNA represent less than 1% of the genome. Moreover no function has been ascribed to them (perhaps they are negative or positive regulators of gene expression?) Third, many studies iindicate that 50-70% of the genome is transcribed as primary transcripts - so are…
apalazzo | December 29, 2007The scientific finding of the year has to be the reprogramming of adult somatic cells into induced pluripotent stem cells (IPS cells). In reality the ground breaking work was published in 2006, however at that time it was not yet clear whether IPS cells were the real thing.
In 2007 IPS cells were indeed shown to be totipotent in the sense that an entire animal can be generated from IPS cells. It is true that for this to occur, IPS cells must be injected into a tetraploid blastocyst, but generally, IPS cells are functionally equivalent (in mouse) to embryonic stem cells. If you start looking…
apalazzo | December 11, 2007Since the discovery of IPS Cells, the stem cell field has exploded. Here's a few links on the latest developements.
First, two cool papers came out recently.
In the first from the Jaenisch lab, mouse IPS Cells were differentiated into erythrocytes and used to cure sickle celled anemia in a mouse model. This would be a first application of these IPS cells in a therapeutic setting.
In the second paper from the Yamanaka group, mouse and human IPS Cells were created by overexpressing 3 of the 4 genes used in the original protocol. In fact the gene that was omitted in this new protocol is myc,…
apalazzo | December 4, 2007Well I'll give you our "author's summary", a feature that accompanies every PLoS paper so that it can be better understood by the lay person:
In eukaryotic cells, precursors of messenger RNAs (mRNAs) are synthesized and processed in the nucleus. During processing, noncoding introns are spliced out, and a cap and poly-adenosine sequence are added to the beginning and end of the transcript, respectively. The resulting mature mRNA is exported from the nucleus to the cytoplasm by crossing the nuclear pore. Both the introns and the cap help to recruit factors that are necessary for nuclear export…
apalazzo | December 2, 2007... and I'm not there. If there's anything noteworthy, please leave a comment.
P.S. This is one of the biggest science meetings of the year, but no press ever goes there and most pop-science journalists are unaware of the meeting's existence. In contrast, both Nature and Science are featuring the Cell Nucleus on their covers, no doubt just in time for ASCB. Are there any ideas out there why this major meeting is under the radar?
P.P.S. Those reviews and papers on the nucleus are pretty impressive - I'll try to blog about them in the near future. Also you should check out Tom's review on…
apalazzo | December 1, 2007Wow! One of the biggest findings of the year! I'll have to read the article more carefully before I comment on it - previously, I wrote a post on the paper that led to this new discovery that was just published online in Science.
Switching from Repression to Activation: MicroRNAs Can Up-Regulate Translation.
Vasudevan S, Tong Y, Steitz JA.
AU-rich elements (AREs) and microRNA target sites are conserved sequences in mRNA 3'-untranslated regions (3'UTRs) that post-transcriptionally control gene expression. Upon cell-cycle arrest, the ARE in tumor necrosis factor-alpha (TNFalpha) mRNA is…
apalazzo | November 29, 2007This week, I haven't had too much time to blog, but I would like to point out two posts written about a paper that I briefly mentioned in a post that appeared last week. It's on that that fabulous result concerning ribosomes from budding yeast.
Background: the S. cerevisiae genome underwent a duplication event - as a result many ribosomal proteins are now encoded by two distinct genes. Two groups located here at Harvard Medical School (the Silver and Roth labs), have found that these critters take advantage of the many duplicate genes that encode ribosomal proteins to construct at least two…
apalazzo | November 21, 2007Yesterday was an action packed day. I got to lab early and made a major discovery. Then last night we had an excellent NERD Club meeting. Then as I walked into the front door at 9PM last night, my wife asks me "Did you hear the news?" Sure enough they have been able to make induced pluripotent strem cells (IPS cells) from human cells. Fantastic. As a biologist, I consider the very first and second experiments on mouse cells to be much more important, and the extension of the technique to another mammalian cell as being secondary.
Now a couple of additional points.
1) From initial rumours it…
apalazzo | November 7, 2007If you have the time, pick up a copy of the latest Nature. There is a paper that describes how a lab, based here at Harvard Medical School, used a random gene splicing strategy to express various fluorescent proteins in each neuron inside of the brain of a transgenic mouse. As a result of the random splicing event (using a cre/lox recombination system), each neuron expressed a different subset of the fluorescent proteins. Here is an example of the brainbow mouse's mosaic brain:
So, how many distinguishable colors did the different cells express?
To determine [the number of distinguishable…
apalazzo | November 6, 2007
One reason that microscopy is such an important tool for biological research is that biological entities function in part through their organization. Just take a look at any micrograph and you will see order, organization and compartmentalization.
But much of the organization that produces biological activity is yet to be uncovered. To highlight this I'll just point out a recent paper on mRNA distribution within a developing embryo.
In this study (published in a recent issue of Cell, see cover left), researchers embarked on a large scale analysis of mRNA localization in developing Drosophila…
apalazzo | October 29, 2007Last week I saw an awesome lecture by Gaudenz Danuser who has a lab at the Scripps institute in San Diego. It has taken me a week to fully digest what was said, plus I haven't had the time to jot this down.
Over the past few years the Danuser lab along with Claire Waterman-Storer's group (see this post and then this post) have used speckle microscopy in order to figure out how the actin cytoskeleton is reorganized during migration. In the process they've really made quite a bit of headway in figuring out how cells crawl.
Actin is just cool. It is the main polymer responsible for shaping the…
apalazzo | October 18, 2007So I heard about this PNAS paper all summer long but never got around to reading it until yesterday.
Neutrophils are white blood cells, whose job it is to chase around invaders that enter your bodily fluids. They can sense foreign invaders by sensing chemical traces. Thus the chemical traces are said to be chemoatractants for the neutrophils. A couple of weeks ago I showed you a movie of a migrating neutrophil chasing a bacterium. Here it is again:
It turns out that if you uniformly stimulate migration by giving the cells a uniform dose of chemoatractant, cells start to migrate in seemingly…
apalazzo | September 17, 2007I've written much about the Nuclear Pore Complex (NPC). This large molecular gate controls the flow of molecules into and out of the nucleus. Recent work (see this post and this new paper) describes how filaments containing "FG repeats" form a matrix in the center of the pore that blocks the movement of large but not small particles. To cross the pore (the black blobs in the pic below), big macromolecules must associate with factors (or nuclear transport receptors, NTRs - red blobs) that can melt and become part of the matrix (the squiggly spaghetti strings).
From a top-down view, the NPC…
apalazzo | September 15, 2007One of the most watched cell biology videos of all time. A neutrophil uses chemotaxis to chase a bacterium around a field of red blood cells. Notice how the neutrophil can suddenly change direction. This clip was shot over 50 years ago by David Rogers at Vanderbilt University.
apalazzo | September 12, 2007(Disclaimer: this is not my field but the paper looked interesting so here goes ...)
Promoters, enhancers and other DNA regulatory elements that turn on or off gene transcription are important. We've known this for quite a while. Many would argue that metazoans all have the same major gene families. Getting closer to us, most vertebrates have the same types of cells and have very similar genes and gene counts. That is not surprising as most genes encode the different tools that go into making the each major cell type found in all vertebrates. To rephrase this idea in a different manner (so…
apalazzo | September 5, 2007Sorry for the lack of posts. I've been reconstructing the figures and the text of my manuscript and expect to resubmit the darn thing to PLoS Biology later this week. Until then here is an interesting paper that I've read recently:
Hitoshi Nakatogawa, Yoshinobu Ichimura, and Yoshinori Ohsumi
Atg8, a Ubiquitin-like Protein Required for Autophagosome Formation, Mediates Membrane Tethering and Hemifusion
Cell (07) 130:165-178
So what's this all about? Well the main player is Atg8, a protein that is essential for forming large multi-vessicular bodies (or MVBs).
What was that?
When cells are…
apalazzo | August 2, 2007Today I will be coming back from our little camping trip (hopefully!) Until I get back to my labtop, I'll entertain you with another post on microscopy.
Flipping through Nature, I stumbled onto this commentary: The good, the bad and the ugly. Here's a taste:
To correctly capture images using a modern microscope, researchers must have a good grasp of optics, an awareness of the microscope's complexity and an obsession for detail. Such skills can take months or even years to master, and yet, owing to inexperience or the rush to publish, are all too often squeezed into hours or days. Popular…
apalazzo | August 1, 2007I'm away camping. Here's another microscopy post from my previous blog.
Well writing a paper makes you feel beaten-up. But now that it's done I feel better. (Hope the reviewers like it).
PS Guess what's I've captured in this image.