Finding Chinks in the Armor: Cancer’s Need for Metabolites

Illustration of energy metablism in cell.Cancer has been studied for decades by scientists trying to find a vulnerability to exploit and testing compounds to develop as potential drugs. As the “Emperor of All Maladies”, cancer has proven itself to be a wily beast with many varieties of genetic mutations for eluding cellular control, tireless in its ability to divide and spread. In the end, a cancer cell is still a cell and subject to its environment even though cancer does not play by the same rules as the normal cells that exist around it. To be able to grow, a cell needs access to metabolites, molecules needed for building the materials and machinery needed by the cell to function and divide. These requirements also offer potential pathways to target for halting cancer growth and spread.

All cells use glucose to generate ATP, but normal and cancer cells differ in how glucose is converted to ATP. Most cells use glucose in oxidative phosphorylation, but cancer cells use aerobic glycolysis, converting glucose to lactate without oxygen. This Warburg effect (glucose converted to lactate) is a hallmark of cancer cells as they take up glucose at a much higher rate than normal cells. Blocking glucose uptake is one way to target cancer cells. While 2-deoxyglucose (2DG) has been shown to slow glucose uptake in vitro, the compound proved toxic in clinical trials and lower dosages do not seem to be an effective treatment against cancer. While not an ideal drug target, glucose uptake has been helpful in monitoring cancer response to therapies via fluorodeoxyglucose positron emission tomography (FDG-PET). Continue reading

Genomic Breakthroughs One Letter at a Time

In honor of Human Genome Month, I delved into our Cartoon Lab archives to retrieve this example of the excitement that occurred while sequencing the Human Genome Project.

For more entertaining science cartoons, visit our Cartoon Lab.

Science News: Demoting Termites, Monitoring Blood Pressure with Your Smartphone and Finding Amelia Earhart’s Bones

A few science news items caught my eye this week.

Macro image of a termite (Isoptera) found under a rock. Image by Sanjay Acharay via Wikimedia Commons.

Wood-Shattering Revelation: Termites have been recategorized based on genetic and other evidence. Turns out, they are just social cockroaches and thus, have become part of the cockroach order Blattodea rather than remaining in a separate order. This decision was not made lightly, but based on years of debate amongst American entomologists. The insects will still retain termite in their name, but they gain a reputation for surviving apocalyptic events. Read about the update to the insect name master list by the Entomological Society of America.

Sphygmomanometer with cuff, used to measure blood pressure via Wikimedia Commons.

Blood Pressure Measurements at the Tip of Your Finger: A blood pressure cuff is bulky, annoying but accurate for monitoring the effort needed for pushing blood around your body. While this device is a fairly simple one, in the developing world it is not that common. However, mobile phones are available to many more globally so why not find a way to put the two together? Turns out that smartphones are equipped with hardware that can be used to measure blood pressure. By adding a device that attaches to the back of a smartphone and with the press of a finger, you can monitor your blood pressure. While not currently as accurate as a blood pressure cuff, the people that tried the mobile blood pressure device were able to quickly adapt to using it, making it easy to take several readings for continuous monitoring. A pocket-sized blood pressure monitor without the nasty squeeze of your arm sounds like a great medical advancement for treating high blood pressure. See a video of the device.

Photo of Amelia Earhart and Dr. Edward C. Elliott, president of Purdue University with the Lockheed Electra she later disappeared in. Purdue University paid for the plane as Earhart was then a consultant on aeronautics there. Photo taken 20 August 1936.

For a Forensic ID, All You Needed Was a Picture, Old Clothing and Some Numbers: The quest to find where Amelia Earhart may have landed in the Pacific Ocean has been investigated and speculated about since she and her navigator disappeared July 2, 1937. In fact, skeletal remains had been found on a remote island in the South Pacific in 1940 along with other artifacts–a woman’s shoe, an American sextant box, but the bones were identified as a man by a physician at the time. Unfortunately, these remains have subsequently been lost. Recently, an anthropologist decided to take the measurements made in 1940, and using a modern-day techniques including a program that estimates stature, sex and ancestry, and he found that the bone measurements were more consistent with Earhart than with 99% of the reference sample used. In addition, using a photograph of the American pilot that had scale generated bone lengths of her humerus and radius and measuring her clothing from a collection gave a number for her tibia. All these numbers strongly suggest the skeletal remains were Earhart’s. Read the press release.

Celebrating Women in Science

By US Environmental Protection Agency [Public domain], via Wikimedia Commons

February 11 is the International Day of Women and Girls in Science, a reminder that there is still a gender gap in science. Despite the obstacles that women need to overcome, their contributions to field of science have benefited not only their fellow researchers but also their fellow humans. From treatments for diseases to new discoveries that opened up entire fields, women have advanced knowledge across the spectrum of science. Below is a sampling of the achievements of just a few women. What other living female scientist or inventor might you add?

Hate malaria? You can thank Tu Youyou for discovering artemisinin and dihydroartemisinin, compounds that are used to treat the tropical disease and save numerous lives. Her discovery was so significant, she received the 2015 Nobel Prize in Physiology or Medicine. Continue reading

Two Epigenetic Targets Are More Effective Than One

Lysine-specific histone demethylase 1 (LSD1) via Wikimedia Commons

Epigenetics is a new and exciting territory to explore as we understand more about the role it plays in gene silencing and expression. Because epigenetic regulation of gene expression is caused by specific modification of histone proteins (e.g., methylation) that play a role in disease states like cancer, enzymes like histone deacetylases (HDACs) become viable drug targets. One drawback to inhibiting proteins that modify histones is even when selectively targeting HDACs, the effects can be far ranging with multiple HDAC-containing protein complexes found throughout the cell. These broad effects minimize the effectiveness of an inhibitor, caught between efficacy and toxicity. A recent article in Nature Communications explored how using a single compound to target two epigenetic enzymes was more effective than any individual inhibitor or combination of inhibitors. Continue reading

Where Would DNA Sequencing Be Without Leroy Hood?

There have been many changes in sequencing technology over the course of my scientific career. In one of the research labs I rotated in as a graduate student, I assisted a third-year grad student with a manual radioactive sequencing gel because, I was told, “every student should run at least one in their career”. My first job after graduate school was as a research assistant in a lab that sequenced bacterial genomes. While I was the one creating shotgun libraries for the DNA sequencing pipeline, the sequencing reaction was performed using dideoxynucleotides labeled with fluorescent dyes and amplified in thermal cyclers. The resulting fragments were separated by manual loading on tall slab polyacrylamide gels (Applied Biosystems ABI 377s) or, once the lab got them running, capillary electrophoresis of four 96-well plates at a time (ABI 3700s).

Sequencing throughput has only increased since I left the lab. This was accomplished by increasing well density in a plate and number of capillaries for use in capillary electrophoresis, but more importantly, with the advent of the short read, massively parallel next-generation sequencing method. The next-gen or NGS technique decreased the time needed to sequence because many sequences were determined at the same time, significantly accelerating sequencing capacity. Instruments have also decreased in size as well as the price per base pair, a measurement used when I was in the lab. The long-prophesized threshold of $1,000 per genome has arrived. And now, according to a recent tweet from a Nanopore conference, you can add a sequencing module to your mobile device:

Continue reading

Hot Wings and Snow Birds: A Study of Genetic Selection in Chickens

African chicken breed Boschvelder. Image copyright ICBH GROUP.

This past summer, I visited the county fair and stopped by the animal barn to look at some of the poultry on display. Specifically, I wanted to see examples of the breeds of chickens available that I may be interested in adding to my flock. Rather than each chicken in their display cage being labeled with a bird’s breed, each cage listed the geographic origin of the chicken within such as Asiatic, Continental or American. This did not benefit my search for potential new members of my flock, but intrigued me enough that I wanted to find out how my flock of 19 hens and pullets would be characterized. Using the classes delineated by the Wisconsin State Fair, my feathered ladies break down to 12 American, 4 English and 3 Continental chickens. There are also classes for Mediterranean and Asiatic (and Other). I live in a part of the United States that gets cold, snowy weather for what seems like six months out of the year, weather that my chickens seem to take in stride. But in other places in the world, heat is the name of the game for the poultry strutting there. In a Genes, Genomics, Genetics publication, Fleming et al. wanted to know if there were genetic differences in Northern European and African chickens that might be caused by their environment. Continue reading

Reveal More Biology: How Real-Time Kinetic Cell Health Assays Prove Their Worth

What if you could uncover a small but significant cellular response as your population of cells move toward apoptosis or necrosis? What if you could view the full picture of cellular changes rather than a single snapshot at one point? You can! There are real-time assays that can look at the kinetics of changes in cell viability, apoptosis, necrosis and cytotoxicity—all in a plate-based format. Seeking more information? Multiplex a real-time assay with endpoint analysis. From molecular profiling to complementary assays (e.g., an endpoint cell viability assay paired with a real-time apoptosis assay), you can discover more information hidden in the same cells during the same experiment.

Whether your research involves screening a panel of compounds or perturbing a regulatory pathway, a more complete picture of cellular changes gives you the benefit of more data points for better decision making. Rather than assessing the results of your experiment using a single time point, such as 48 hours, you could monitor cellular changes at regular intervals. For instance, a nonlytic live-cell reagent can be added to cultured cells and measurements taken repeatedly over time. Pairing a real-time cell health reagent with a detection instrument that can maintain the cells at the correct temperature means you can automate the measurements. These repeated measurements over time reveal the kinetic changes in the cells you are testing, giving a real-time status update of the cellular changes from the beginning to the end of your experiment. Continue reading

Postcards from the Northern Roman Empire

Some of the thin wood tablets found at Vindolanda in Northumberland, England. Image Copyright The Vindolanda Trust.

Correspondence whether via postcard or letter has been a method of human communication likely since people became literate. Old letters and postcards have been uncovered in attics, basements and garages, offering depth and richness to historical events or adding context to how humans lived in the past. But what about finding correspondence from more than a few hundred years ago?

Interestingly, archeologists were excavating in a Roman fort just south of Hadrian’s Wall and discovered well-preserved thin slices of wood with ink writing dating to the 1st century. While these 25 postcard-sized correspondence, found in a line about 3–4 meters long, are just the latest uncovered at the Vindolanda fort, the documents add to the history of Romans in Britain.

Many of the newly discovered wooden wafer postcards seemed to contain complete messages and could be read without the need for infrared photography. This treasure “hoard” of ancient Roman writing tablets offer insights such as a man named Masclus asking for leave. His previously discovered correspondence also from the Roman fort at Vindolanda included asking his commanding officer to supply more beer to his outpost.

The announcement of these 25 new Roman messages by the sponsors of the fort excavation are only preliminary overview of the find. In fact, archeologists are working on conserving and deciphering messages on the wooden tablets and plan on using infrared photography to reveal if there is any more writing on these postcards from the past.

Read more in the Vindolanda Trust Press Release.

Six (and a Half) Reasons to Quantitate Your DNA

Knowing how much DNA you have is fundamental to successful experiments. Without a firm number in which you are confident, the DNA input for subsequent experiments can lead you astray. Below are six reasons why DNA samples should be quantitated.

6. Saving time by knowing what you have rather than repeating experiments. Without quantitating your DNA, how certain can you be that the same amount of DNA is consistently added? Always using the same volume for every experiment does not guarantee the same DNA amount goes into the assay. Continue reading