Author: Sara Klink

Long-Lasting Beauty from the Humble Egg

Posted on by Sara Klink
Egg tempera image of multiple people surrounding a dais - Panel by Fra Angelico
“The Coronation of the Virgin” tempera on panel by Fra Angelico [Public domain], via Wikimedia Commons

Chicken eggs are widely found in most grocery stores. They are a cheap and unassuming source of protein, easy to cook as you desire (e.g., fried, scrambled, hard boiled) or use as a binder for other food items (e.g., meatloaf, cakes, cookies). One reason I keep laying hens myself is not only for fresh eggs but also to have egg shells other colors than white, the predominant color sold in US grocery stores. However, did you know that these humble eggs have uses that don’t end up in the stomach and instead, are a feast for the eyes? I was introduced to the concept of egg tempera, a medium used for painting, by my colleague, Karen Stakun, artist and manager of our graphics department during a discussion about chickens. I was intrigued by the concept.

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In Defense of Wild Spaces in the Yard

Posted on by Sara Klink

Pale purple asters and milkweed. Copyright S. Klink.

Surrounding my mowed lawn is a wild, mostly uncultivated space that currently has goldenrod blooming with tall asters starting to blossom. Every day when I pass these flowers, I see bumblebees, butterflies and other insects collecting the nectar to eat or store for the winter. Last year, when a section of soil was disturbed during construction of a building, I decided to seed the area with native wildflowers rather than grass. (I am not a fan of mowing the lawn.) Watching the series of flowers bloom over the late spring to autumn has been beautiful, colorful and full of tiny moments of joy. Not only do I see insects enjoying the flowering plants, but birds will land on the taller greenery, sometimes just resting, sometimes collecting seeds. I am not sure who has been startled more often, me or the birds when I walk by, flushing a bird from the thicket of tall plants.

Monarch butterfly on thistle photographed in the prairie at Promega headquarters in Madison, WI. Copyright Promega Corporation.

Where some people might see wild, unruly areas, I see Monarch butterflies on their daily flight, fluttering above me and the “weeds”. I have even been lucky enough to find Monarch caterpillars munching on milkweed, a common plant in my wild space. Despite my efforts, I have a lot of tall ragweed appearing in my yard, but have discovered that birds love the seeds, including my chickens, and squirrels will remove and eat the leaves. In addition, I see fireflies in early June through late August, many I find hanging out on the shady greenery during the day before their light display at night. Continue reading “In Defense of Wild Spaces in the Yard”

How Autophagy Feeds Cancer’s Need for Metabolites

Posted on by Sara Klink
Illustration of energy metablism in cell.

Metabolism underpins numerous cellular processes. Without it, cells would not grow, divide, synthesize or secrete. Another pathway, autophagy, degrades unwanted cellular materials, helping to maintain cell health. With these opposing roles, is there a connection between autophagy and metabolism? As it turns out, the answer is yes. Because molecules degraded by autophagy are recycled and fed into metabolism pathways as precursor compounds. There are interesting implications as a result of this connection, ones that affect cancer cells as described in a recent Cell Metabolism review article.

Autophagic flux, the process by which molecules and organelles are directed to the autophagosome, fuse with the lysosome and are degraded, involves a selective process that determines the cargo carried within the autophagosome. Autophagy-related genes (ATGs) direct the process and particular receptor proteins bind the cargo. What is interesting about the connection among cancer, autophagy and metabolism is the complexity of the role that autophagy plays in cancer. While autophagy was thought to act in a more tumor suppressive manner as shown when one copy of an ATG6 analogous gene in mice was deleted and the other left unaltered, and malignant tumors developed, but in mice mosaic for ATG5 deletions, the inhibition of autophagy resulted in benign tumors in the liver. This latter experiment suggested autophagy was needed for cancer progression, a hypothesis reinforced by the lack of ATG mutations in human cancers.

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

Posted on by Sara Klink
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).

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Celebrating Women in Science

Posted on by Sara Klink
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 in science. 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.

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Two Epigenetic Targets Are More Effective Than One

Posted on by Sara Klink

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 “Two Epigenetic Targets Are More Effective Than One”

Where Would DNA Sequencing Be Without Leroy Hood?

Posted on by Sara Klink

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:

Welcome to the future – DNA sequencing on your mobile phone – imagine where and how you can use it. Hats off to the @nanopore team for getting this to work at this form factor, voltage and watts. https://t.co/Tm6A5fj8M4

— Ewan Birney (@ewanbirney) November 30, 2017

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

Posted on by Sara Klink
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.

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

Posted on by Sara Klink

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