Friday, August 30, 2013

Thank You Anthony Pawson for Your Contributions to Cell Biology

Ribbon diagram of the SH2 domain. 
Anthony Pawson, a Cell Biologist who was instrumental in determining how cells communicate, died at the age of 60 in Toronto Canada. Pawson is best known for determining the SH2 domain and its role in cell-to-cell communication. His research was instrumental in finding new classes of drugs to treat a variety of ailments including cancer, diabetes, and autoimmune diseases. 


You can also learn more about Dr. Pawson's research from his laboratory's web page.

Thursday, August 29, 2013

CLARIOstar is Showcased at ELA in Hamburg Germany

The new CLARIOstar&reg high performance microplate reader with Triple Detection Technology - filters, spectrometer, and new advanced LVF MonochromatorsTM - was recently shown at the European Laboratory Automation conference in Hamburg Germany.

The CLARIOstar&reg is the perfect multimode microplate reader that does not compromise on sensitivity, speed, or flexibility. It is the only microplate reader with Triple Detection Technology, and it is the only microplate reader with next generation LVF MonochromatorsTM. The LVF MonochromatorsTM, being based on linear variable filters, have filter-like performance in sensitivity and in bandwidth flexibility (8 to 100 nm adjustable bandwidth).

Click here to watch E.J. Dell discuss BMG LABTECH's new CLARIOstar&reg microplate reader.


Find our more about the CLARIOstar&reg here. 

Wednesday, August 28, 2013

Fun facts: On this date in science history


Goethe by Georg Oswald May  
On August 28th, 1749; Johann Wolfgang von Goethe was born. In addition to poetry, Goethe had an intellectual interest in science, especially; zoology, botany and geology. He coined the term morphology to describe the systematic study of the structure of living things and agreed with evolution; viewing the origin of plants and animals as the specialization and differentiation throughout time to their present forms. However, in many instances we can now say he should have concentrated more on his poetry. His theory on color disagreed with Newton's interpretation of white light as a mixture of colors and he saw all plant structures as modifications of leaf forms.

Tuesday, August 27, 2013

FAQ: Why is there a gender bias in autoimmune diseases?

It has been known for some time that females can mount a more powerful immune response than males. While this is usually beneficial, it also means that females are more susceptible to auto-immune diseases such as type 1 diabetes. By definition an autoimmune disease is one in which your immune system identifies your cells as foreign and mounts an attack to eliminate them. In type 1 diabetes insulin-producing cells of the pancreas are destroyed leading to increased blood glucose.

The structure of insulin
A recent paper in the journal Immunity entitled: 'Gender Bias in Autoimmunity Is Influenced by Microbiota' indicates that both microbes and hormones play a role in gender bias for type 1 diabetes. The authors from The University of Chicago employed several different mouse strains that were grown under various conditions. They found that mice grown in germ-free conditions did not exhibit gender bias and that mice with some types of defined microbiota, that were overrepresented in male mice, did support gender bias. Furthermore they show that androgens, male hormones, influence gut microbiota and could work as a positive-feedback mechanism that contributes to the gender bias of autoimmune disease.

Monday, August 26, 2013

Did you know: New mouse models faithfully recapitulate human prion diseases

Research performed at the Whitehead Institute in Massachusetts has led to the creation of mouse models for both Creutzfeldt-Jakob disease (CJD) and fatal familial insomnia (FFI), two fatal prion diseases that effect humans. As with other prion diseases CJD and FFI are caused by mutations in the prion protein that result in a misfolded protein. This misfolded protein can induce normal prion protein (PrP) to assume this shape and build up in clumps of protein containing many misfolded prion proteins.

Immunohistochemical staining of cerebellar tissue of a
patient that died of CJD in the US.


Previous to this report, entitled: 'Profoundly different prion diseases in knock-in mice carrying single PrP codon substitutions associated with human diseases' animal models that mimic the disease process in humans were not available. In order to create these the models the scientists used a knock-in approach where the mutated human prion sequence for each disease replaced the normal mouse PrP. They found that as a result of this approach the effect of FFI mutation was neuronal loss in the thalamus and CJD mice exhibit spongiosis in the hippocampus and cerebellum as is seen in humans.


This report in PNAS is just the latest exciting development in prion disease research. We at BMG LABTECH have been glad we can play a small part in prion research when our FLUOstar Omegas are used in RTQuIC assays that can be used to screen for the presence of misfolded PrP in a variety of samples from several species.

Friday, August 23, 2013

Focus on: Events

The CLARIOstar from BMG LABTECH

Don't forget to sign-up for the BMG LABTECH / Promega webinar entitled: Enhanced Protein-Protein Interactions in Living Cells Using the NanoBRET™ Assay from Promega and the CLARIOstar's LVF Monochromator.

It will take place Wednesday August 28, 2013 at 11:00 AM ET.

To preregister visit:



We hope you can join us!

Thursday, August 22, 2013

Applications Thursday: Viral Replication Assay's

Electronmicrograph of Herpes virus.
by 
George W. Beran


In the recently published PLoS Pathogens article entitled: 'A Systematic Analysis of Host Factors Reveals a Med23-Interferon-gamma Regulatory Axis against Herpes Simplex Virus Type 1 Replication' a group of European collaborators use the POLARstar Omega from BMG LABTECH to assess viral growth. They do so using viruses that have had fluorescent protein sequence incorporated into their genetic material. The result is they are able to assess growth over time to gain an understanding of the role of host factors at all stages of the virus life cycle.



Since they wanted to monitor the effects 7,237 human genes they needed the capabilities of the POLARstar Omega that allowed them to perform higher through put and use 384 well plates. Since they were monitoring cells for the effects over time; from 24 hours to 80 hours post infection; the optional Atmospheric Control Unit (ACU) is very beneficial in these types of studies. The ACU allows you to control carbon-dioxide and oxygen levels in addition to the temperature control which is standard on the POLARstar Omega.

For more information on the POLARstar Omega and other microplate readers from BMG LABTECH please visit our website: www.bmglabtech.com

Wednesday, August 21, 2013

Fun facts: On this date in science history

Larry Page & Sergey Brin
by Graziano Origa (pen & ink)
On August 21st 1973 Sergey Mikhaylovich Brin was born. Sergey is the Russian-American computer scientist who, along with Larry Page, co-founded Google, Inc. in 1998. The name Google was a play on the word googol, the mathematics term for a huge number; one followed by a hundred zeros. This term was used to reflect the company's mission to organize the vast information available on the web. In a relatively short time Google has grown in value and influence; I am sure that few of us could imagine a world without Google search capabilities.

Tuesday, August 20, 2013

FAQ: Are there any new targets for treating bacterial infections?

Incidence of Brucella infections in animals during the first half
of 2006
(green-never reported; blue-not reported in this
period; brown-confirmed clinical disease; red-confirmed
infection; grey- no information

by Flukeman


In the case of the debilitating chronic form of the bacterial disease brucellosis, the answer is yes; according to a recent paper in Cell Host & Microbe. The paper entitled: 'PPAR-Mediated Increase in Glucose Availability Sustains Chronic Brucella abortus Infection in Alternatively Activated Macrophages' is the result of work by scientists at UC Davis. Brucellosis, which primarily affects people from the Mediterranean and Middle East, is typically the result of ingesting unsterilized milk or contacting the secretions of infected animals.

The paper reports that the scientists identified the cells that harbour B. abortus during persistent infection as a recently identified immune cell known as alternatively activated macrophages (AAMs). They also found that the metabolism of the AAMs is altered such that the B. abortus is supplied with glucose that allow for the survival of the bacteria and the resulting chronic infection.

This alteration in metabolism is induced by peroxisome proliferator activated receptor  (PPAR). PPAR now represents a target that can be inhibited thus starving the bacteria. As proof of principle the paper reports that treatment with a PPAR inhibitor significantly reduced AAMs and B. abortus in infected mice while treatment with a PPAR activator increased bacteria.

Monday, August 19, 2013

Did you know: Scientists have found a gene which could increase efficient biofuel production

Ball-and-stick model
of cellulose Ibeta

by
Ben Mills
Biofuels are an increasingly attractive energy resource as the already limited availability of fossil fuels continues to dwindle. Biofuels are derived from the sugars of plants; and fast growing plants, such as poplar and eucalyptus trees and various grasses, represent the best source for these fuels. Within plants the cellulose of the cell walls is what needs to be accessed in order for biofuels to be produced. Cellulose is a long chain of smaller sugar molecules called glucose. Cellulose can be converted to this glucose and used in classic fermentation to produce alcohol.

There is, however, another component of the cell wall called lignin which essentially holds the cellulose together and gives firmness to the plant that allows for their upright stature. Lignin also, unfortunately; in the eyes of a biofuel producer; reduces the accessibility of the sugar in the cell wall, thus limiting biofuel production potential.

Now, a group of international scientists have identified a gene that is important for lignin production. Their results are reported in the Science Express article entitled: 'Caffeoyl Shikimate Esterase (CSE) Is an Enzyme in the Lignin Biosynthetic Pathway' The authors found that when CSE is non-functional 36% less lignin is produced and the remaining lignin had an altered structure. In the final analysis; conversion of cellulose to glucose was increased 4 fold in plants with mutated CSE.

The authors now hope to identify plants with mutated CSE or to embark on genetic engineering in order to have a stock of plants with non-functional CSE which can be employed in the production of biofuels.

Friday, August 16, 2013

Focus on: events

The CLARIOstar from BMG LABTECH features an
advanced linear variable monochromator
On August 28th at 11:00 AM EST BMG LABTECH and Promega will co-present a webinar entitled: Enhanced Protein-Protein Interactions in Living Cells Using the NanoBRET™ Assay and CLARIOstar®. In this webinar you will learn about how you can measure protein-protein interactions in living cells and how the new CLARIOstar microplate reader can help you to enhance all of your assays.

E.J. Dell, PhD will speak on behalf of BMG LABTECH and the speaker from Promega will be Thomas Machleidt, PhD.

If you would like to join us for the webinar you can register at:
https://vts.inxpo.com/Launch/QReg.htm?ShowKey=14343


Monday, August 12, 2013

Did you know: The peak of the Perseid meteor shower is tonight?

Perseid meteor (8/12/09)
by Nick Ares
It is believed that humans around the world have observed the Perseid meteor show every year from around July 17th to August 24th for at least 2,000 years. The best time to see this years shower will likely be from the late evening on August 12th to the morning of August 13th when as many as 60 meteors an hour could be seen.

Meteors are the result of small particles that enter the atmosphere which heat the air around them resulting in the characteristic streak of light. The material for these meteors comes from the Comet Swift-Tuttle but in the night sky the comets appear to originate from the constellation of Perseus hence the name Perseid.

In order to best see the shower you should get away from city lights, if possible, then get comfortable in a reclining chair and look up! Unlike other celestial events your eyes are the best tool for viewing a meteor shower.

Friday, August 9, 2013

Focus on: Epigenomics

DNA molecule that is methylated on both strands on the
center cytosine

by Christoph Bock

The human Roadmap Epigenomics Project is an NIH funded project which seeks to perform global analysis of changes in gene activity and expression that are not dependent on gene sequence. Although each cell in the human body contains the same genomic information; encoding about 25,000 genes; each cell type expresses these genes differently. Epigenetics is believed to be the major force behind the differences between cell types due to different cell types having a different pattern of methylation. Methylation is, chemically speaking, the addition of a methyl group that marks the DNA any time a cytosine resides next to a guanine in the DNA sequence (CpG's). The result of this marking is differential packaging of DNA and distinct DNA sequences being available for expression in each cell type.

A recent paper entitled 'Charting a dynamic DNA methylation landscape of the human genome' is a major milestone in epigenomics as it shines light on when, where and how many CpG's participate in genomic regulation. The group mapped most of the 28-million CpG's found among the 3-billion nucleotides that make up human DNA in 30 different cell and tissue types. The majority of the sites are unchanged but the ones that are changed are in locations that are likely important for gene expression. Now that they have identified these differentially methylated regions (DMR's) they believe they will be able to perform more directed methylation analysis on these regions. This means they will not have to perform complete sequencing on all of the more than 200 different human cell types but can instead concentrate on these DMR's and still discover the differences between the cell types.

Thursday, August 8, 2013

Applications Thursday: Reactive oxygen species detection

E. coli


Production of reactive oxygen species (ROS) is an important part of a hosts response to an infection. Examples of ROS include oxygen ions and peroxides that can damage bacterial cell structure. Analysis of ROS production was one of the factors studied in the recent paper 'Comparison of host response mechanisms evoked by extended spectrum beta lactamase (ESBL)- and non-ESBL-producing uropathogenic E. coli' which was published in BioMed Central Microbiology.


ROS-production was monitored with a luminol-horseradish peroxidase (HRP) assay using the FLUOstar Optima microplate reader from BMG LABTECH. In this assay luminol is activated by hydrogen peroxide and the resulting luminescence is proportional to ROS-production. The authors found the ESBL-producing bacteria produce higher levels of ROS and that this correlates with the decreased virulence of this bacteria.

The luminol-HRP assay is one of many approaches available to assess ROS levels. BMG LABTECH application notes have previously described other luminescent (lucigenin) or fluorescent (DCFH) probes that similarly monitor ROS levels. These approaches are suitable for use on all the classes of microplate readers from BMG LABTECH such as the Omega, PHERAstar and CLARIOstar.


Wednesday, August 7, 2013

Fun fact: Better sunscreen possible using bioprospecting

"Drontheim Fjord"by Karl Kaufmann


Bioprospecting is a branch of science that tries to find organisms that have traits that may be useful in industrial applications. Norwegian researchers, using this approach, have identified a species of bacteria that live in the Trondheim Fjord that produce a pigment that can absorb long-wavelength UV radiation. Long-wavelength UV radiation is associated with multiple forms of skin cancer, so incorporating the pigment from this bacteria into sunscreen would provide unprecedented protection from harmful solar radiation.


The bacterium in question is named Micrococcus luteus and contains a carotenoid called sarcinaxanthin which absorbs sunlight at the appropriate wavelength to have the desired affect for a sunscreen. A Norwegian company named Promar AS has patented the production of sarcinaxanthin and have given it the commercial name UVAblue. Promar AS have isolated the gene that produces the pigment and produced recombinant bacteria in order to produce large quantities of UVAblue. The goal now becomes; finding a more cost-effective means of production to reduce the cost of UVAblue.


Tuesday, August 6, 2013

FAQ: What are 'driver genes'?

Within a tumor many genes may be mutated, but not all of these are necessary for the cancer to continue to grow. The genes that are most responsible for a cancer to remain a cancer are called driver genes. Due to their importance in cancer, driver genes are the best targets for therapy. However, until recently, identification of the driver genes for a particular tumor was not possible.

Mouse neurons labeled with fluorescent tags
by Stephen J Smith
source:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693015/



In the recent Nature Genetics paper entitled: 'The integrated landscape of driver genomic alterations in glioblastoma' the authors describe an approach which identified 33 different driver genes that are responsible for the most prevalent and aggressive form of brain cancer. The majority of these genes are not currently targets of any available drugs. However, when drugs become available the authors envision personalized glioblastoma treatment becoming a reality. This would involve identification of which driver gene is responsible for the individuals brain cancer and then application of the appropriate treatment.




The search for inhibitors of these driver genes is possible with appropriate assay design and analysis both of which are possible with the multimode readers available from BMG LABTECH. Please visit our website (www.bmglabtech.com) to find out more about the capabilities of our microplate readers.

Monday, August 5, 2013

Did you know: Scientists have solved the structure of NatA which modifies most human proteins

Protein crystals grown in space:
A collage of protein crystals many of which
were grown on the U.S. Space Shuttle. All the
crystals are useful for X-ray diffraction analysis
by NASA
NatA, a member of the N-terminal acetyltransferase family of proteins, is an enzyme complex that appears to be essential for the growth of cells. NatA modifies nearly 50% of all other proteins by adding an acetyl group which plays a role in regulating the function of the various proteins. The acetylation of proteins has been shown to regulate protein activity, sub-cellular localization and stability, as well as other protein fuctions. The role of NatA in this process is especially intriguing due to the number of proteins it is capable of modifying and the fact that NatA expression is elevated in cancer cells.

A recent Nature Structural & Molecular Biology paper entitled: 'Molecular basis for N-terminal acetylation by the heterodimeric NatA complex' describes the work which resulted from a colaboration between scientists in the USA and Norway. They employed X-ray crystallography and solved the structure of the entire NatA complex and the structure of the catalytic subunit alone. They found that binding of an auxillary protein induces a conformational change in the catalytic subunit which essentially acts as a switch that turns on the enzymatic activity.

Because of the numerous proteins affected by NatA, and its association with cancer, the authors now seek to identify small molecule inhibitors for NatA. The solved structure will allow them to compare this enzyme to other enzymes with known inhibitors. These inhibitors can then be used as the basis for a directed approach to screen for inhibitory compounds. In order for a compound screen to be performed an enzyme specific assay will need to be designed that can be used in high throughput screening.

The CLARIOstar
BMG LABTECH has a number of microplate readers that are suitable for assay design and high through put screening. The CLARIOstar is our new microplate reader that features a LVF monochromator. This monochromator distinguishes itself from others with its ability to continuously adjust band passes and excellent monochromator sensitivity. These characteristics make it outstanding for the design of fluorescence and luminescence assays.

In order to perform high through put screening you want a microplate reader that is both sensitive and fast. The PHERAstar FS is our most powerful microplate reader whose specialty is high through put and can save you time and money by reducing reagent costs.


For more information on how these and other microplate readers from BMG LABTECH can help you with assay design and high through put performance please visit our website: www.bmglactech.com

Friday, August 2, 2013

Focus on: Saving the orange through DNA modification?

In the NY Times article: A Race to Save the Orange by Altering Its DNA Amy Harmon reports on the huge toll that Citrus Greening has taken on orange crops around the world. This disease is caused by the bacterium C. liberibacter which are transferred from plant to plant by insects called psyllids as they feed on the sap in orange tree leaves. Thus far all efforts, which include increased use of pesticides and burning of infected plants, have failed to have any effect.

The idea of altering the DNA of a plant or animal, particularly when it will be consumed, is unthinkable to some; especially if it is done in a lab. When a plant or animal has had its DNA scientifically manipulated it is commonly referred to as a genetically modified organism (GMO) which have a highly negative connotation. Activists propose that GMO's should be labeled as such but companies are reluctant to do so because of the negative perception of GMO's.

 Adult Asian citrus psyllid, Diaphorina citri,
 (2-3 millimeters long) on a young citrus leaf

by David Hall
Supporters of the use of GMO's point to the fact that cross-breeding of similar plants and animals and selection of individuals with desirable traits is how we have the relative diversity of agricultural products that exist today. Recognizable products like corn and orange-colored carrots are the result of this selection. The orange itself is the product of cross-breeding. They also believe that much of the fear of GMO's is based on the general public not understanding DNA. As an example of this lack of understanding; the NY Times article cites a 2004 survey that indicated that more than 50% of those surveyed believed that if the DNA for a gene from a fish is used in a tomato it will cause the tomato to 'taste fishy'.

In the end, the orange is running out of time. The traditional selection process will likely be too slow to respond and without assistance the orange will disappear. But if making a GMO orange is the only answer, will the public want it?

Thursday, August 1, 2013

Applications Thursday: Multiplexing Fluorescence and Absorbance to Monitor Protein Transport

Green Fluorescent Protein (GFP).
by Richard Wheeler


In a recent paper from Frontiers in Microbiology the Swiss authors demonstrate the multi-mode capabilities of their FLUOstar Omega microplate reader from BMG LABTECH. They used a reporter system that consisted of a promoter that was sensitive to their protein of interest linked to GFP. In this way the could monitor the movement of their protein of interest across the membrane as well as metabolism of their protein of interest indirectly through changes in GFP expression. In order to normalize for cell number between the different mutants tested and over the 7 hour time course of their experiment they also used absorbance at 600 nm to measure cell turbidity. Just another way a multi-mode reader from BMG LABTECH can simplify your experiments!


The majority of the microplate readers that BMG LABTECH offers are multi-mode capable, including the PHERAstar FS and the new CLARIOstar, any one of which could perform similar analysis to serve your purposes.