Entries in Science (9)

Monday
Nov142016

A Primer on Hormonal Hunting on World Diabetes Day! 

 

As a diabetic, I dread the feeling of hypoglycemia. It happens when I spend hours in the lab and forget to eat, when I overestimate my appetite and give too much insulin or when I exercise without making sure to give my body some extra sugar. Non-diabetic colleagues of mine claim to know the feeling of just craving sweets, feeling week and being unable to focus. I don’t know if they fully understand how it feels though when you break into cold sweat, you feel like you can’t hold yourself upright and certainly can’t keep your thoughts organized. It’s awful. So awful, evolution decided that it would be a great way to weaken prey and make it easier to hunt!
Snails aren’t exactly fast enough to catch fish under normal circumstances, but cone snails use venom to disorient small schools of fish and use their extended mouth like a net to catch their prey. Conus geographus and Conus tulipa, two cone snail species, have been found to use a very remarkable strategy to disorient their prey – they target their energy metabolism to induce hypoglycemic shock. The component of their toxin that is responsible for that reaction in fish is a modified version of insulin. Interestingly, the peptide is much more similar to fish insulin than the mollusk’s own, yet bears the typical posttranslational modification signature of the snail’s usual toxins. 
While I certainly empathize with the poor fish who die in this dreadful manner, I would very much die without insulin and am therefore very thankful to the founders of Genentech, who enabled humanized insulin production through their recombinant DNA technology which is now used by Eli Lilly to keep millions of diabetics healthy and happy. For humans insulin isn’t exactly a great weapon: A review from 2009 stated that only 66 cases of homicide by insulin have been reported, in which 11 needed an additional weapon. As I said… It’s slow and painful, but definitely gives you enough time for a 911 call. 
MGS
1) PNAS 2015 112(6), 1743-8
2) Drug Test Anal 2009 1(4), 162-76
Wednesday
Oct262016

Happy Halloween!

To get into the Halloween spirit this weekend, my roommates and I carved pumpkins. We had a lot of fun as we carefully cut out our designs, while trying to preserve our fingers! However as you know, before you get to the fun of carving there is a lot of prep work to be done. Our pumpkins produced A LOT of pumpkin “guts”. We didn’t want to waste all of this, so we decided to roast the seeds. YUM, this definitely was a good decision!  I was curious as to the nutritional value of pumpkin seeds and I learned they are a great source of protein, fiber, zinc, etc. In fact, a research study was published this summer by XJ Zhao et al. suggesting pumpkin seed oil (PSO) can alleviate certain types of cellular damage caused by a high-fat diet in rats1. This study divided rats into three groups: 1) controls fed a normal diet (n=20), 2) a high-fat diet group (n=20), and 3) a high-fat diet group with PSO intervention (n=20). Liver tissue samples were examined by histology and quantitative real-time PCR. The PSO intervention group showed decreased accumulation of fat deposits in the liver, as compared to the high-fat diet group1. Further, the PSO intervention group displayed normalized expression patterns of genes involved in lipid metabolism and inflammation, as compared to the high-fat diet group1. While it is unknown whether these results will translate to humans, consider roasting pumpkins seeds as you celebrate Halloween this year!

-TMG

1) Zhao et al. (2016) Intervention of pumpkin seed oil on metabolic disease revealed by metabonomics and transcript profile J. of Science of Food and Agriculture

Friday
Jul152016

When Two Wrongs Make a Right

Poliovirus, which was once a serious threat to the lives of many, is now playing a vital role in the fight against the deadliest types of brain cancer. A genetically modified version of the poliovirus has been used to treat some cases of glioblastoma, a type of brain cancer that kills its victims within two years on average[1]. Dr. Matthias Gromeier, a molecular biologist at Duke University, is credited with the discovery of the modified poliovirus. Over the course of 5 years, there have been a total of 22 patients who have used the poliovirus as an attempt to cure their glioblastoma with 11 deaths and 11 patients recovered or in remission[2]. Despite the high number of deaths, the drug is held in high regards because it has shone a light on future advancements in cancer research.

            The poliovirus was chosen because its receptor, cluster of differentiation 155 (CD155), is commonly found on most tumor cells. This discovery prompted scientists to try using the poliovirus to kill tumor cells. However, in order for that treatment to be successful, the disease-causing ability had to be removed from the virus. The development of the genetically modified strain of poliovirus, which is called PVS-RIPO, requires the internal ribosomal entry site (IRES) of the poliovirus to be replaced with the IRES of the human rhinovirus 2[3].This slight change does not completely alter the functions of the poliovirus, but reduces its intensity, preventing damage to the nervous system and accidental death of the patient. This is important to the success of PVS-RIPO. When injected in the body, the virus attacks the cancerous tumor cells and partially kills the cancer. The rest of the work is done by the immune system, which attacks the site of the poliovirus and thus the tumor[4]. As the immune system works to kill the disease, the tumor size increases and appears to worsen over the span of two months. Eventually the inflammation decreases and the tumor slowly disappears, placing the patient in remission. A safe remission period is defined as 6 months without any signs of a tumor, which has become a fairly common result of patients using the poliovirus strain.

            Although there will need to be improvements made to the PVS-RIPO treatment, there are still many accomplishments to look forward to. Many patients are still in remission up to 36 months after treatment, which is unheard of for cases of glioblastoma2. Looking into the future, Dr. Gromeier and his colleagues at Duke are hoping to test this virus on other types of cancer to determine the versatility of PVS-RIPO4.

-  LR


[1] "Glioblastoma (GBM)." American Brain Tumor Association. American Brain Tumor Association, 2014. Web.

[2] Pelley, Scott. "Killing Cancer." CBS 60 Minutes. CBS Interactive Inc., 29 Mar. 2015. Web. 24 May 2016.

[3] Goetz, Christian, and Matthias Gromeier. "Preparing an Oncolytic Poliovirus Recombinant for Clinical Application against Glioblastoma Multiforme." Cytokine & Growth Factor Reviews 21.2-3 (2010): 197-203. Web.

[4] Gromeier, Matthias, MD, and Gordana Vlahovic, MD, MHS. "Targeting Cancer with Genetically Engineered Poliovirus (PVS-RIPO)." The Preston Robert Tisch Brain Tumor Center at Duke. Duke University Health System, 2016. Web. 26 May 2016.

Thursday
May052016

Prion-like proteins help guide plants to know when to bloom

With flowers blooming and plants finally producing their first leaves of the season, it can make one ask the following: how do plants know when to bloom? Scientists at the Whitehead Institute of Biomedical Research may have a lead on this question.  While studying Arabidopsis thaliana, they identified over 500 proteins in the species that have potential prion-like domains (PrDs). Of all of these proteins, Luminidependens PrD was one of the proteins that had traits similar to prions and could play a role in the plant’s response and memory with regards to seasonal environmental changes.

Prion proteins are thought to give a unique ability of biochemical memory, which has been studied in both mammals and fungi. Before the researchers at Whitehead discovered the Luminidependens PrD, there had been no known prions that existed in a plant model. When this protein was tested in a yeast model, it displayed all the functions of the yeast prion Sup35, which has been extensively studied. This PrD formed higher-order oligomers, which is similar to the function of prions in the yeast model.

 

The conformational switches that prions catalyze can lead to a variety of different outcomes. These scientists believe that in plants, the prions can aide in the response to seasonal changes and events, such as flowering every spring. The ability for plants to have a “memory,” from year to year is thought to be possible through the use of prions.  From season to season, plants will respond and regulate themselves differently based on their past experiences. Based on the researchers’ findings, these conformational changes in the proteins seem to be evolutionarily conserved and according to the researchers, could extend beyond the flowering and into different biological processes as well.

 

Chakrabortee, Sohini, et al. "Luminidependens (LD) is an Arabidopsis protein with prion behavior." Proceedings of the National Academy of Sciences (2016): 201604478.

Tuesday
Apr192016

The rise of Pharming in Agriculture

Plants have been used for the treatment of diseases for thousands of years – long before researchers were able to identify and purify the active compounds. Salicin, which is found in willows, is a great example of such a compound. The bark and leaves of willow trees were being used to treat fevers and headaches around 400 B.C. However, it wasn’t until the 1800s that scientists discovered the active compound in willow trees (salicin) that conferred those beneficial properties.

In the last few decades, scientists have started using plants differently for the treatment of diseases. Sijmons et. al. demonstrated that gene insertion is possible in plants by showing that tobacco and potato plants could express the human serum albumin protein. This process of gene insertion is now referred to as pharming (a combination of “farming” and “pharmaceutical”). Initially, the field faced many challenges, including disapproval from anti-genetic-modification movements and regulatory uncertainty. Low yields as well as purification cost were other hurdles faced and it wasn’t until around 2009 that pharming obtained a realistic opportunity for commercial development. In 2012, the first pharming product (taliglucerase alfa, used for the treatment of Gaucher’s disease) was approved for use in humans. This attracted major pharmaceutical companies such as Mitsubishi Tanabe Pharma, which acquired Medicago (plant-based vaccines developer) in 2013.

 

The major benefit of pharming is that it does not require expensive infrastructure, as the plants are generally grown in an open environment. This enables the production capacity to be increased, by keeping the cost low. However, like any other process, pharming also has disadvantages. A major environmental concern is pollination/seed contamination. Other risks include accidental entry of the drug into food chains and consumption by non-targeted organisms.

Personally, I think there is still some way to go before pharming becomes the “go to” method for large-scale drug production. But interest in the process has increased exponentially in the past few years, suggesting that it has the potential to become an important technique in drug development.

~AKHD

P. Sijmons et. al. (1990) “Production of correctly processed human serum albumin in transgenic plants” Biotechnol. 8:217-21.

E. Stoger et. al. (2014) “Plant molecular pharming for the treatment of chronic and infectious diseases” Annu Rev Plant Biol. 65:743-768.