The risk for men getting cancer in their lifetime is 1 in 2 and for women it is 1 in 3. It is well understood that cancer is a major health threat. While sometimes cancers can be “cured” by surgery, chemotherapy, radiation therapy, or at the very least, prolong life, there is no cure for all cancers at this time. Cancer research has been underway for decades, and it is undeniable that progress has been made in developing treatments for cancer.

Could the key to curing some types of cancers lie in understanding the functions of certain growth factors and cytokines? There are several growth factor based cancer therapies available today. Avastin®, an Anti-VEGF antibody, prolongs life by preventing blood vessel formation. Aldesleukin (The recombinant laboratory produced form of IL-2) stimulates the immune system and has been shown to cure 6% of renal cancers. While Herceptin® and other cancer drugs have targeted epidermal growth factor (EGF) and its regulation of the cell cycle. It seems that even though cancer cells may over-express or have “mutated” growth factors, normal cells also require the presence of the same growth factors. In addition, not all cells within a given tumor exhibit mutations for a given growth factor.

These drugs, like most cancer drugs, have serious side effects and this of course limits their effectiveness and use. Is there a growth factor or cytokine perhaps yet to be discovered, that is uniquely and universally expressed in cancer cells? Is there another approach you feel is more likely to be a cure for cancer? Let us know you thoughts.

 
Structural proteins in addition to being the most abundant class of proteins in nature and contributing to a cell’s morphology and function are also used for a number of alternative applications.  Below are three common structural proteins and a description of their practical functions. This raises the questions: How many other applications are structural proteins already being used for?  What other innovative applications can structural proteins be applied to in the future? 

Fibrin-  Bandages that contain fibrin that functions by providing a protective matrices to accelerate blood coagulation therefore hindering blood flow.  Full story.

Keratin-  The primary fibrous structural protein component of hair, skin and nails can be used to clean up oil spills.  This natural absorbant adheres the oil removing it from the water.

Collagen-  Used as a surgical adhesive to cover and seals wounds.  Full Story.

List of other structural proteins:

Actin, Actinin, Aggrecan, Biglycan, Cadherin, Clathrin, Decorin, Elastin, Fibrinogen, Fibronectin, Heparan, Laminin, Mucin, MAG, MBP, Myosin, Spectrin, Tropomyosin, Troponin, Tubulin, Vimentin, Vitronectin

YFG powered by Ingenuity was a great first for Sigma, and from the looks of it we’ve managed to break some ground for Life Science according to bloggers at the Fisheye Perspective and Bitesize bio.
These bloggers have reviewed the website and found it to their liking.  They even help us out by pointing out some improvements.

Feel free to make your own suggestions for Your Favorite Gene in the comments section below or send them to yfgsuggestions@sial.com.

Kristy Meyer - Customer Interface Specialist  kristy.meyer@sial.com

Although text-messaging and social networking web sites have dramatically influenced the way humans coordinate their activity, bacteria are one step ahead of us with their unique ability to communicate via quorum sensing.  This type of communication results in prokaryotic phenotype modification based on the density of the communicating population.  Bacteria use quorum sensing to effectively coordinate decision-making between non-centralized groups of like or unlink bacterial species.  As part of the communication process, signaling molecules called autoinducers are secreted in levels proportionate to the overall cell population.  As the threshold autoinducer concentration is met, specific bacterial genes are expressed.   The expression of these genes results in phenotypic changes involving sporulation, biofilm formation, conjugation, bioluminescence, and virulence.

It has been hypothesized that if the quorum sensing network of the pathogenic species was targeted rather than the over employed targeting of the species itself, the risk of resistance would be minimized.  Recent quorum quenching research on various Vibrio species and E. coli strains has identified several anti-infective protein targets, specifically enzymes and transcription factors.  For example, a bacterial enzyme, 5′-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) is directly involved in synthesizing the autoinducers key to quorum sensing.  Additionally, several acyl-homoserine lactone-inactivating enzymes have been described in the literature.  Reported quorum sensing inhibitors are 3-oxododecanoyl-homoserine lactone analogs and brominated furanones, while transition-state analogs to select human catalytic antibodies are also capable of degrading bacterial quorum-sensing molecules.

For more details on this interesting communication tool, please view Dr. Bonnie Bassler’s  iBioseminar.

Current commercial versions of preformulated protease inhibitor cocktails all contain variations of common sets of the classical inhibitor products.
 
AEBSF: Serine Proteases
Aprotinin: Serine Proteases
Bestatin: Aminopeptidase
EDTA: Metalloproteinases
E-64: Cysteine Proteases
Leupeptin: Serine and Thiol Proteases
Pepstatin A: Acidic/Aspartic Proteases
Phosphoramidon: Neutral Endopeptidase
1,10-Phenanthroline: Metalloproteinases

Such standard formulations work well for many applications, but most certainly cannot totally eradicate all unwanted proteolytic activities for every application.  In addition, many other classical inhibitors are typically left out.  For instance a2-macroglobulin is often recognized as one of the most broad-spectrum protease inhibitors, yet it is rarely utilized as a protective inhibitor. 

 
While Sigma scientists have invested considerable resources to formulate the most effective cocktails suitable for as many applications as possible, each cell line, extraction/purification procedure and expression system poses a different set of proteolytic challenges.  Please share your experience if you have encountered problems with standard cocktail formulations or have developed novel strategies for protease inhibition.

The detection of single molecules opens up new perspectives in structural biology, cell biology, and biotechnology. Single molecule studies are one of the hottest topics in biological sciences because they bring us closer to understanding cellular processes. In some cases an entirely new understanding of the functioning of biological machines is revealed. An interesting aspect of this technique will be to measure features of individual molecules that are masked in ensemble measurements. An important goal of single molecule studies is the 3-D-visualization in real-time observation of single molecules in live cells, relative to in vitro studies.
The need for ultra sensitive and specific biomedical diagnostic tools calls for the development of optical and photonic technologies capable of reaching the single bimolecular level as well probes with desirable spectral and luminescent characteristics, e.g. small size, high quantum yield, high extinction, reduced photobleaching and blinking.
Fluorescent detection of single molecules in photophysics was first demonstrated in 1989. Only a few years later, new methods brought single molecule fluorescence into the area of biology. Researchers are constantly improving single molecule technologies and it will undoubtedly play a prominent role in future cell studies. Share your thoughts about the future and benefits of interdisciplinary single molecule studies.
Read more in the comprehensive Essay by
R.D. Vale, Cell, issue 135, page 779 – 785 (2008)

Regardless of their field of study, life scientists face some common challenges when they sit down to analyze their data and design their next experiment.  They wonder whether they asked the right question – whether they have all of the key players on their radar - and whether they have a good understanding of the ripple effects of perturbing their system.  This is where knowledge-based pathway tools such as Ingenuity Pathways Analysis can lend a strong hand in generating relevant, testable hypotheses.  Pathway analysis tools address those challenges head on by enabling life scientists to ask targeted questions about biological and chemical systems, and visualize the answers to those questions in a dynamic graphical interface.

·         What are the key molecules involved in a particular pathway?

·         What lies upstream?  Downstream?  Is there a binding partner that would be easier to modulate or that has a better expression profile?

·         How can I intervene in this pathway to affect a particular cellular or disease phenotype?

·         What are the secondary effects that lie downstream of that intervention?  Can I design an assay to measure that readout?

·         What are the molecular paths that lead from a genotype to a phenotype?  Which of those paths are most relevant to my tissue of interest?

·         What lies just around the corner from this pathway – should I include some of those players in my readout?

In answer to those questions, pathway analysis helps life scientists narrow in on the genes, chemicals and pathways most relevant to their experimental system, and make more confident decisions about which direction to take next.

So, how can pathway analysis tools enable your research?

In December 2007, the Time Magazine published “Top 10 Scientific Discoveries of 2007” and #1 is the most recent “induced pluripotent stem cell (iPS cells) breakthrough, in which two groups simultaneously published results of using four particular stem cell-associated genes in retroviral vectors to “reprogram” human skin cells into embryonic stem cell-like cells.

The development of iPS cells is also the #1 advancement in the field of Regenerative Medicine. The use of iPS cells in place of ES cells derived from human embryos has brought tremendous enthusiasm to this field. This would be an avenue to create an unlimited supply of ES-like cells bypassing the current issues. Many believe that iPS technology has enormous possibilities for safe and ethical treatment of numerous diseases.

However, there are several critical challenges concerning the use of iPS cells in therapeutic applications in humans. The most immediate challenge involves the tumorigenic potential of the use of retroviral infection. The second challenge is comparably low efficiency of the reprogramming process due to lack of decent knowledge about the mechanisms by which reprogramming occurs. Another risk is associated with c-Myc, one of the genes used in reprogramming; whose over expression may cause cancer. There are also technical difficulties in creating safe and plausible differentiation capabilities to guide the iPS cell lines down a desired lineage. Recently, scientists from the Harvard Stem Cell Institute published a study in which adult cells were infected with adenoviruses as the vehicle to transport the genes associated with the pluripotency. Other studies have shown that use of small molecules for induction of iPS that may replace the need for gene transduction.

Although it was developed less than 2 year ago, the iPS technology has exhibited unprecedented promises for research on a better understanding of nuclear reprogramming and therapeutic applications. Currently, researchers are generating iPS cells from individuals with identified medical conditions, creating both personalized and disease specific cell lines. In the future, the huge potential of stem cell research may be realized without the use of embryos, since iPS technology does not require donated IVF embryos or human eggs. Also, iPS cells allow for personalized medicine as both the nuclear and the mitochondrial DNA matches that of the donor. Other than the mentioned benefits, iPS cells would not require any immune suppression, which made them a superior choice over ES cells for therapeutic uses.

In his acceptance speech for the Rosalind Kornfeld Award for lifetime achievement at the 2008 Society for Glycobiology meeting, Dr. Robert Spiro used the analogy of a museum with ongoing, multiple rooms of discovery to describe the field of glycobiology. What an excellent metaphor! Identification and understanding of oligosaccharide structure has led to biosynthetic pathways, and the recognition of pathway involvement has now linked carbohydrates and glycans with cellular signaling and cell development.

Glycobiology research is no longer just examining glycans to locate where they are and what they do. It is also being looked at from the opposite direction – starting with diseases including cancer, diabetes, Alzheimer’s disease, HIV, and multiple sclerosis. Medical researchers are starting to ask how glycobiology relates to their work – if specific oligosaccharides could act as biomarkers, how carbohydrates modulate signaling, or what profile changes in a glycan pool might function as positive or negative indicators of disease development.

Collaboration has provided in-depth knowledge of specific techniques to answer research questions that cannot be fully answered using a single investigative route. Because glycan synthesis and modification are not template-based reactions, a spectrum of analytical techniques is being used to tease out functional-structural relationships.

Gene silencing, knockout mice, western blots, glycan microarrays, and enzymatic and chemical cleavage techniques are some of the methods actively being used. Mass spectrometry has been applied to glycan analysis with expertise; several posters and presentations at the conference included MS data prepared by collaborative experts in the field. Chemical synthesis of unnaturally modified sugars contributes to innovative research applications. Add on top of that the medical expertise necessary to study specific disease states, and there’s a synergy between glycobiology, glycochemistry, and medicine that will drive future communication and collaboration.

Did the Glycobiology Conference get you thinking about the impact of glycobiology on medicine? Please share your thoughts.

Current dietary nutritional research continues to provide important insight about the molecular interactions of nutrients and their individual roles in systems biology, but are these pinpoint details causing humans to make poor food choices? We are faced with an overabundant and sometimes contradictory source of nutritional information. Are information overload and limitless selection of food making us susceptible to decisions based on convenience rather than our instinctual dietary requirements?

In comparison, the simplistic concept of caloric restriction (CR) for enhanced longevity and prevention of disease seems rudimentary and may be considered a disregard for dietary guidelines.  However, evidence from CR studies documents alzheimer’s, atherogenesis, cancer and diabetes prevention and supports the theory that aging may be slowed. The benefit of CR is linked to sirtuins, NAD+-dependent deacetylases that are activated when cell energy is depleted.

The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies. Maalouf, M.A., Brain Res. Rev. (2008).

The role of calorie restriction and SIRT1 in prion-mediated neurodegeneration. Chen D., Exp. Gerontol. (2008).

Sirtuins: novel targets for metabolic disease in drug development. Jiang, W.J., Biochem. Biophys. Res. Commun., 373(3), 341-344 (2008).

Caloric Restriction in Rhesus Monkeys