What causes Alzheimer’s?

http://www.nytimes.com/2014/03/20/health/fetal-gene-may-protect-brain-from-alzheimers-study-finds.html

This article focuses on the recent studies done with REST, a gene regulator that seems to have a more active role in Alzheimer’s than previously believed. It’s articles like these that make me glad I’m a science major, since I can actually understand what’s going on! I’m more and more often surprised (and delighted) with how much we’ve already learned.

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Balm ingredients

I recently came across a product at the drugstore that I’ve been meaning to try out. But before I decided to buy it, I did some research. Some of you may have heard of “Bag Balm”. It comes in a little green tin and runs for about $10, claiming to heal chapped skin and fight infection. Although I can attest to neither, I’ve heard people say that it works. The ingredients list read: ACTIVE INGREDIENTS: 8-HYDROXYQUINOLINE SULFATE 0.3% in a PETROLATUM, LANOLIN BASE. Thanks to orgo, I know how to picture 8-hydroxyquinoline! It’s function is very interesting as well. Apparently, it binds to the surface of bacteria and fungi and creates a toxic compound, poisoning and thus killing the organisms. Related structures are being tested as potential antibiotics against drug-resistant bacteria.

However, it seems that you may get more than what you bargained for, with Bag Balm. Up until a few decades ago, mercury was one of its active ingredients. I know back when science wasn’t as advanced, people even used mercury to treat syphilis, or some similar disease. These pharmaceutical mishaps make me question whether there has been enough research done on some of the products we use everyday and their long-term effects.

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Science Comics!

In light of a recent discussion on the possibilities today of “playing” with molecules and adapting them to our needs, I decided to share a comic from one of my favorite webcomics (though I really like “Hark! A Vagrant” as well, Lynn!):

 

Just because we can doesn’t always mean it will turn out well. 🙂

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Cool DNA gif!

tumblr_mnmun27hml1rv2z05o1_400

 

I came across this gif (hopefully it’ll show up) of how RecA works! RecA is an Ecoli protein which among other things catalyzes the formation of chiasma during replication and repairs damage that occurs during recombination. Defects in the protein can cause DNA damage, and weird recombination (which I discovered the hard way when I was cloning). Anyway, I thought the gif was cool!

 

Edit: The gif works if you click on it!

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GUYS!! SCIENCE!!

http://www.washingtonpost.com/news/morning-mix/wp/2014/04/11/lab-grown-vaginas-successfully-implanted-in-girls-in-tissue-engineering-first/?tid=hp_mm
Essentially, four females with a disease that prevented formation of their sexual organs, got lab grown vaginas (made from their own cells) implanted into them. So, as long as everything continues to go well, they are now able to have children!
This is, I think, one of the first times a organ that was grown in the lab is able to be successfully transplanted. Ahh the implications of this research!

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Mirror-Imaged Nucleic Acid Enzymes

This week, we spent some time talking about A-DNA, B-DNA, and Z-DNA and how the individual nucleotides are able to twist in specific directions but not others. I know I also wondered why only only one direction is allowed, why is that twist more favorable over another. Maybe you have always wondered the same thing as well!

I came across an article linked below about a group of scientists that have successfully created mirror image enzymes, called Spiegelzymes, which are made of nucleic acids. (Maybe there isn’t really a distinct line to separate proteins and nucleic acids, instead they can come together to perform a more important function in different organisms.) These enzymes can be used in living cells for the targeted cutting of natural nucleic acids, basically as molecular scissors. They are also very stable and, most importantly, do they do not trigger side reactions of the immune system. These nucleic acid zymes could cut up individual nucleic acids responsible for human diseases and thus deactivate them, which can be potentially incorporated in a drug to stop the spread of certain diseases!

 

http://www.genengnews.com/gen-news-highlights/looking-glass-nucleic-acid-zymes-promise-rna-editing-wonderland/81249442/

 

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Those biochemically literate cancers

I love it when material from different classes comes together! This week, I did a presentation on drug resistance in my cancer genomics class looking specifically at a drug that targets a fusion protein that is a product of a chromosome translocation. Thinking back to the information storage property of DNA, one can easily see how having pieces of DNA from different chromosomes fused together combines two templates which are transcribed and translated into a single protein whose structure and hence function are different from either original protein. The protein  formed in this case was Bcr-abl an over active kinase which leads to leukemia.

Using bioinformatics, scientists have been able to come up with a structure of a drug (Gleevec) that fits into the active site of the kinase and binds it so it can no longer perform its phosphorylation function and the cancer can be slowed down. The unfortunate thing however is that the cancer cells (as if they know biochemistry) mutate residues that are important for electrostatic interactions between the drug and the kinase to uncharged ones , or replace small residues with bulky ones  creating an inability for the drug to bind and leading to drug resistance by the cancer cells.

I’m glad that concepts from different classes come together to give me a better understanding of varied concepts.

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Do Life Like Watson (or better yet, learn from his good traits and let’s leave some of those other unmentionables behind)

By this point, we’ve all established our opinions on Watson. Some of them have been somewhat unflattering. But, I watched a TED Talk (posted below) in which I thought he had some interesting research (life?) advice as he elaborated on how he and Crick “discovered” the structure of DNA.

His biggest piece of advice? Build models.

Or, specifically, Watson encourages us to not be afraid to be wrong, to entertain the wrong concept and to learn from the process. (As biochemistry majors, I suspect we are Type A enough to rarely feel comfortable with falsehood.) By getting out every idea possible, we give ourselves creative license to eventually figure out the answer. It’s a bit of no shame, no gain!

Secondly, he tells us to not be the smartest person in the room. As we saw in the movie last week, Watson and Crick would have been no where without the research and expertise of others in genetics, including Rosalind. However, back then, Rosalind was an X-Ray Crystallographer–part of a highly specific field for which she did not necessarily have an expert understanding of biochemistry. While Watson and Crick really didn’t seem to do much research, perhaps, they did manage to scoop everyone else–and benefit from the scientific community’s expertise!

This brings me to another point, which is Communicate (with a Capital C). In lab, we will all present–if we have not done so already–and Watson emphasizes the importance of such effective scientific exchange in part by admitting he successful beat Rosalind to the DNA structure because she didn’t talk about her work with anyone else. (Or, this could be his artistic license when he told his story.)

All this is nice and lovely for a blog post, you say, but where’s the science? Well, Watson went on to discuss his current work, wherein his research team has found that people with autism and schizophrenia often miss entire gene sequences. You can just imagine all the biochemistry involved (phosphodiester bonds and phosphodiesterases, for one)! He didn’t get into this science, of course, but it is interesting to think of where these studies could lead us…

In fact, it seems that many of my “how life works” questions are still unanswered by biochemistry. How and why do these specific gene sequences become removed in autistic and schizophrenic people? What biochemical therapies can we develop to counteract all that? This is what being a biochemist is all about!

See the TED Talk: How we discovered DNA by James Watson

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Embryonic Stem Cells

When we were watching the DNA sequencing video a thought struck me. Very early in the video they mention how DNA consists of exons (which code for the proteins) and introns (“junk DNA”?).

I took the Intro to Stem Cells course my first year, and learned of the different type of stem cells. Obviously, The First (fertilized) Cell must be capable of differentiating into anything, and thus have chemical signals to change what sections of DNA make up introns, and which ones should be activated for exons.

A basic search of “stem cells and exons” did not bring up any research on such specificity. Then again, I’m sure it’s not easy to research. Also, the nature of stems cells means that they would have to be researched in vitro, which could of course change pathways.

I’d be curious to hear if anyone else knows more!

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Pyrosequencing!

We have been discussing Sanger DNA sequencing recently, so I wanted to talk about another method of sequencing that was used in a lab I worked in – pyrosequencing!

When I first heard of it, I assumed it had something to do with fire, but actually the “pyro” in the name comes from the fact that pyrosequencing involves the detection of pyrophosphates!

pyro

Essentially, pyrosequencing works by adding a primer to the DNA and then introducing it to nucleotides one at a time, and measuring DNA polymerase activity after nucleotide introduction through measurements of pyrophosphate release.

Since the nucleotides must add in order starting from the primer, by adding nucleotides one at a time (and degrading them immediately afterwards) and seeing which one results in an increase in pyrophosphates, you can find the sequence of the DNA strand. You can even tell if there are a few in a row based on the “intensity” in the peak of polymerase activity.

It is always incredibly exciting to hear about new technologies that make it even easier to get to the “meat” of the questions we’re trying to answer!

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