Traditionally, when you're interested in studying a gene or want to use it in a fancy molecular construction, you have only one option : molecular cloning techniques which are (very) time consuming. Recently, Gene production techniques emerged; they are relatively rapid (turnaround ranging from 2 weeks to a month or more, for more complicated construction) but very expensive (1.5$ / basepair... so a pricetag in the thousands is not uncommon). The technique involve oligo synthesis and stitching by PCR; it work well for small genes, but large constructions can be problematic. Researchers at the University of Michigan just invented a way to easily build genes using a microfluidics approach.

The University of Manchester has put up a free, web-based bioinformatics course. It even has an introductory "quiz" asking questions related to the course material (I personally scored 50%, which I consider to be quite an achievment; some questions are very tough / obscure). Of course, bioinformatics is a very large field, covering very differents topics (microarrays, sequence analysis, structure prediction, databases, etc), and EMBER doesn't cover all these topics. I recommend it to anyone interested in bioinformatics, even if its just to check what the field is about.

Even if SARS is a distant memory (from last year), research is still ongoing to understand this deadly virus. Californian researchers determined by X-Ray spectroscopy the 3D structure of the RNA genome of SARS. They found unusual and very interesting features, including a rare 90 degree bend. The unique structure could be a promising target for future drug development against SARS.

Affymetrix, owner and inventor of the GeneChip technology, just took a big step forward with the approval by the FDA of their first system intended for clinical use, the 3000Dx. Apparently, the system will be used to provide in vitro clinical genotyping, such as the Roche AmpliChip(TM) CYP450 Test, which allow "... diagnostic laboratories to identify certain naturally occurring variations in the drug metabolism genes, CYP2D6 and CYP2C19. These variations affect the rate at which an individual metabolizes many common drugs used to treat diseases including depression, schizophrenia, bi-polar disorder, cardiovascular disease treated with beta-blockers and others. Knowledge of these variations, when considered with other contributing factors, can help a physician select the best drug and set the right dose for a patient sooner, as well as avoid drugs that may cause the patient to suffer adverse reactions." The in vitro genotyping market powered by microarray is developing fast and the competition is fierce, but currently Affymetrix got the best microarray technology (by far).

If you're into qRT-PCR, Premierbiosoft's Beacon Designer (a primer-design software) version 4 just got released. Lots of primer design programs are available on the web, but this one is specialized in qRT-PCR (SYBR green primers, dual-labeled taqman primers and probes, molecular beacons).

First whole week of vacation time since last year (at the same period), and I can't say I don't appreciate it :) I found an internet connection (dial-up... soooo slow) so I can post news again. In this period of , I want to express my gratitude for the support and interest you've shown for this blog. I'm considering moving to a .com domain (still have to decide to keep TheScientistBlog or to switch to another name) with MovableType instead of Blogger as a platform. Blogger is nice with the free hosting and all, but it has several limits for my purpose. If you have suggestions, the discussion forum is online with 2 users (counting me!) :) Happy Holidays everyone! P.S. : As many surfers interested in bioinformatics come from India, a special thought for those in the Indonesia-India region who got hit by the earthquake / tsunami... I lived throught a very minor flood, compared to a tsunami... so I can try to imagine what you're living throught.

Some hope for a Melanoma (skin) cancer cure : researchers from the Dana-Farber Cancer Institute (Boston) discovered that this particular type of cancer is dependant on a cell cycle control protein, CDK2. The finding suggest that by cutting off the supply of this protein, cancerous cells would be unable to multiply; it wouldn't destroy the cancer, but inhibit its growth.

Got programming skills? Wanna get involved in Bioinformatics? SourceForge got a whole category devoted to bioinformatics, with lots of active open-source projects going on and needing some help. Microarray and mass spectrometry data analysis, 3d molecular visualization, sequence assembly and alignement, the list goes on and on... Get involved : open-source development is a very good thing for the scientific community.

Molecular evolution - how did it arise? How did all these proteins aquire their (in some case multiple) functions? A new study published in Nature Genetics shed some light on the subject. They simulated evolution by mutating multiple-functions proteins, to see if all functions were affected at the same time and to gain a better understanding of evolution.

Today version 3.3 of Genomatix popular in silico promoter analysis suite got released. Notable quote from their mailing list press release : "We are currently writing up a paper about a very promising approach to micro array analysis, which has now many times proved to be successful in identifying small sets of co-regulated genes. The strategy includes identification of involved TF binding sites and framework construction leading to regulatory network analysis. If you would like to know more on that, just let me know. I can send you a explanatory Powerpoint presentation." Can't wait to see what its about... Microarray analysis would greatly benefit from a biologically accurate co-regulation analysis package. It would help to build hypothesis about regulation mechanism (which transcription factor is likely to be involved, which signalization cascade, which receptor / pathway, etc). Changelog available in the full post for those who are interested.

More news from the Harvard Medical School : "A new study provides evidence that a herpes vaccine developed by a Harvard Medical School researcher is a strong candidate for testing in humans. The study, published online Dec. 14 in the Journal of Virology, compared three different experimental vaccines for herpes simplex virus 2 (HSV-2), the virus that causes most cases of genital herpes."

Researchers from the University of Minnesota found a way to use DNA as a scaffold to build circuits to process or store data. They developped a technique allowing them to assemble DNA in predetermined patterns and create a circuit template. Using special DNA containing docking sites at regular intervals, they can then direct the assembly of microscopic electrical components. Interesting quote : "The scaffolding has the potential to self-assemble components 1,000 times as densely as the best information processing circuitry and 100 times the best data storage circuitry now in the pipeline." Another cool biotechnology application emerging from out-of-the-box thinking.

DNA methylation plays a big role in gene regulation - methylation adds a small "tag" (a methyl group) to cytosine (the "C" letter of DNA) - this "silence" the gene in higher eukaryotes and it don't get expressed. It allows for time/space dependant expression. Until now, enzyme who mediate the addition of the methyl group were known, but not those charged of removing it (to unsilence the gene). Researchers from the Harvard Medical School just found the first one.

From the press release
: "Researchers have discovered an enzyme that plays an important role
in controlling which genes will be turned on or off at any given time
in a cell. The novel protein helps orchestrate the patterns of gene
activity that determine normal cell function. Their disruption can lead
to cancer."

Interesting discovery about the method used by some (positive-stranded RNA) flaviviruses to get prefentially translated by the cellular machinery. It involve a protein complex with a specific 3d structure(instead of a poly-A tail) which cellular enzyme recognize. It could potentially lead to specific inhibitors targeting this class of virus. Press release : "The binding of a viral RNA and a viral protein brings about a physical transformation that dupes host cells into enthusiastically copying the invading pathogen, according to a team of researchers from Harvard Medical School (HMS) and Massachusetts Institute of Technology (MIT). In the December 17 issue of Science, collaborators led by professor Lee Gehrke of the Harvard-MIT Division of Health Sciences and Technology publish dramatic three-dimensional images of RNA-protein interactions in alfalfa mosaic virus (AMV), a safe model for investigating single-strand, positive-sense RNA viruses. AMV's dangerous relatives include flaviviruses that cause dengue fever, Japanese encephalitis and West Nile disease.

"Mymetics Corporation announced today that it has received approval from the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) to begin advanced preclinical testing of the Company's trimeric gp41 vaccine in nonhuman primates. The study will run through the end of the third quarter of 2005, testing the second generation of HIV vaccines in development. Based on the results of the NIH-approved study, Mymetics expects to initiate advanced toxicology testing by the end of 2005 in preparation for filing an Investigational New Drug (IND) application in 2006." Their vaccine approach is based on a concept not generaly accepted in the scientific community : they think that gp41 (HIV protein responsible for fusion with the cell to be infected) "subtly" mimics IL-2, an immune system protein. For this reason, they think that the immune system is somewhat unable to produce effective antibodies against HIV. I can't say I'm convinced by this, but the vaccine approach (trimeric gp41) might be worth trying. However, note gp41 is usually masked by gp120, so antibodies can't easily reach it.

Powerful research tools that speed up vaccine development have led to the start today of human tests for a preventive vaccine against the respiratory disease SARS. The disease killed hundreds of people around the world before it was brought under control in 2003 with aggressive conventional public health measures. Researchers at the Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), will conduct the trials. The experimental vaccine against SARS, or severe acute respiratory syndrome, will be tested on 10 healthy volunteers at the NIH Clinical Center in Bethesda, MD. The clinic will do periodic follow-up exams on each volunteer for 32 weeks.

An international research team has identified immune-system genes that appear to play a key role in the body's defense against HIV, the virus that causes AIDS. The findings may lead to ways of circumventing the virus's ability to avoid vaccines by rapid mutation. The study in the Dec. 9 issue of Nature also describes how HIV infection is driving human evolution, since individuals with protective versions of the identified genes are more likely to survive and pass those genes along to children. Including researchers from the University of Oxford and the University of KwaZulu-Natal in South Africa, the investigation is a result of a program established by the Partners AIDS Research Center at Massachusetts General Hospital (MGH).

UBC scientists have discovered an enzyme in mammals crucial to the transportation of proteins within cells. This discovery opens up new avenues of understanding of the mechanisms underlying the function of neurons and new approaches to therapy for neurodegenerative diseases such as Alzheimers and Huntington Disease.

Party till 3 in the morning + help my girlfriend move (very) early today = exhausted, so today's news are gonna be press release style. The party was a blast : I won two bottle of wine, cinema tickets and the first prize for the center's best article (as second author, but its still nice!). Still have shopping to do today (I'm always late for that). I'll be back tomorrow or late tonight.

Its (already) Christmas time; I have my lab's party tomorrow so don't expect news until Friday! As you can see I added a Google Adsense Search box, which allow to search through the whole site. I'm extremely sorry about those of you who got pop-up ads this week; I have tracked the cause of it to the Bravenet minipoll module, which I promptly remove. Future polls will be in the forum, which I encourage you to join to discuss news / ask questions. Happy Pre-Christmas party for those of you who have one this week, remember : don't abuse of alcohol and chocolate, be careful while driving, and have fun!

Molecular imaging is a field that gained major attention in biology in the past few years, starting with the discovery/isolation of GFP, a protein able to emit (green) fluorescence when excited (for example with a laser). Nowadays, a panoply of fluorescent proteins / chemicals allow for precise tracking of different biological components (proteins, organelles, DNA) when coupled to antibodies or fused with proteins. Pretty covers for science magazines, very useful in the lab, everyones happy! Recent developments in the field include in vivo imaging (in real, live animals) and sequence-specific RNA tracking (with molecular beacons). Both were put to good use by a research team of the Abramson Cancer Center in a study related to cancer.

Washington University of St Louis report that researchers developed a method to gros norovirus in-lab, which is a first. It will lead to a better understanding of the virus and the diseases it induce (gastroenteritis or "stomach flu"). The virus is a very common cause of food poisoning. Using the in vitro cultured virus, researchers were able to determine that it had specific tropism for Macrophages and Dendritic cells, components of the immune system responsible of warning T and B cells that something is wrong (by presenting antigens, usually small peptides of degraded pathogens) and activating the immune response.

California Institute of Technology released today news that computation can be embedded in a DNA crystal, a cute mix of biotechnology and nanotechnology. They designed DNA molecules which specific sequence cause them to crystallize in a pattern of progressively smaller "triangles within triangles," known as a Sierpinski triangle.

Researchers at the Uppsala University (Sweden) are using a computer-assisted strategy for rapid drug design for various diseases. This week they published very encouraging results where they describe the exclusive use of bioinformatics software to develop new potential drug candidates against a newly discovered, essential enzyme of the Malaria-inducing parasite, Plasmodium falciparum.

Fresh bioinformatics / microarray news coming from BMC Bioinformatics (which RSS feed can be found on the right sidebar). GECKO, a free, open source application designed to analyze massive amounts of data coming from high-throughput microarray experiments. I didn't have the chance to try it yet; the binary isn't available for download but will be very soon according to the abstract. You can check the sourceforge project page to download the binary and source when it'll be ready.

The UT Southwestern Medical Center at Dallas must be in full press release mode, cause it's the second major (and interesting!) one they release in a week (AIDS spreading post-oral infection is the other one, which we covered earlier). This time its about gene therapy and skin cancer. Using a mouse model for xeroderma pigmentosum (a genetic disease causing extreme sensibility to sunlight and ultraviolet rays, which cause skin cancer), the researchers achieved the first successful gene therapy for skin cancer (caused by this particular deficiency, it isn't a cure for skin cancer you and me might get).

As you see, I spent the last few days working on the site design. Bigger page with 3 columns optimized for 1024x768 resolution (sorry to the 800x600 guy, you're lone, upgrade your display :)). Previous posts available in the right sidebar for quick scanning of new/past content. Various RSS feeds from popular Biotech news websites so you always have fresh news to chew on. Optimized ads placement. Bigger title bar. Optimized speed and loading times. No more time/budget for explosions/ninjas, sorry! Right now I'm pleased with the new design, except for a small (but annoying) "flash" bug while the page loads. I'm a bit puzzled about this one, so if you're affected too or know how to fix it, let me know in the comments section!

Researchers from the UT Southwestern Medical Center (Dallas) just released the results of a study aiming to understand how SIV (the simian/monkey equivalent of HIV) oral transmission proceed by tracing the presence of viral genomes in various tissues. "By innoculating monkeys with SIV they traced which tissues in the mouth and digestive tract were infected during the first week. Furthermore, they traced which organs and lymph nodes were first infected and uncovered likely routes of infection. The findings are published in the Dec. 3 issue of the journal AIDS." Previously, our understanding of oral infection by SIV/HIV was deficient compared to the usual sexual relation/blood transfusion/Infected Seringe routes. The results define in time and space the spread/speed of oral infection.

An inquiring mind asked me what I thought of this article, revealing the encouraging results of AIDS-related vaccine trials. While the title of the article is highly misleading ("Human Test: Novel Vaccine Stops HIV"), the underlying research is a big step forward in our understanding of AIDS. They're using dendritic cells extracted from the AIDS-positive patient; they prime them with killed virus and reinject them in the patient. Dendritic cells can then go alert the immune system en masse. But don't go think that we found AIDS cure yet!

According to a press release from North Carolina State University, researchers have succeeded in simulating protein-protein interaction by simplifying the model they chose - Amyloid Fibril formation by random-coil peptides - so that only the most important features were conserved, ignoring the others. By doing say, they dramatically reduced the length of calculations necessary to simulate the formation of protein aggregates. Amyloid fibrils are essentially found in diseases like Alzeihmer and Parkinson, which are caracterized by the formation of protein clumps inside cells, which impair normal function of neurons and cause their death. Discovering how fibrils forms may lead to a better understanding of these diseases. Here's the abstract of the soon-to-be-published paper :

Abstract: Assembly of normally soluble proteins into amyloid fibrils is a cause or associated symptom of numerous human disorders, including Alzheimer’s and the prion diseases. We report molecular-level simulation of spontaneous fibril formation. Systems containing 12-96 model polyalanine peptides form fibrils at temperatures grater than a critical temperature that decreases with peptide concentration and exceeds the peptide’s folding temperature, consistent with experimental findings. Formation of small amorphous aggregates precedes ordered nucleus formation and subsequent rapid fibril growth through addition of beta-sheets laterally and monomeric peptides at fibril ends. The fibril’s structure is similar to that observed experimentally.

Sorry for the slow news, but the last few days were quite a rush. To make a long story short, I've finished this week the (complicated) construction of a new virus I'll use in my doctorate (yeah I'm in bioinformatics, but I'm a touch-to-everything kind of guy, and I love the thrill associated with molecular biology). I'm almost a month ahead of schedule, which is a very good thing. About the favicon thing, I noticed that its not working for IE folks because it isn't named favicon.ico... but Mozilla/FireFox can use the .jpg. I'll upload the .ico as soon as I can. The forum will wait, as I got no comments showing interest for it right now. As a last note, ad performance is a little disappointing lately, even tough traffic is increasing nicely, so I might change the layout / position of ads. I hope they stay informative/interesting/targeted without being too evident/annoying. Drop a comment if you got suggestions/feedback about the current design.

In case you didn't notice the little AIDS ribbon on Google frontpage, today 1st December 2004 is World AIDS day, which is about reminding us all that HIV is an issue for everyone. The World Health Organization just released their 2004 AIDS epidemic update (available in multiple languages). The overview inform us that 39 millions people are currently living with AIDS worldwide, with 5 millions new infections and 3.1 millions deaths (including 500 000 children) this year. As you can see, the epidemic is far from being controlled, despite 20 years of intense research and International awareness. Quote from the report : "AIDS is affecting new sections of populations, and an increasing proportion of people are becoming infected through unprotected heterosexual intercourse." People think that they're safe, that antiretrovirals can cure HIV/AIDS. This isn't the case. Protect yourself and be responsible. Get tested if you're at risk.