Theives and Genes and Bears - Oh my!

Tardigrades, also known as "water bears" or "moss piglets", are super robust microorganisms that can survive extreme conditions, such as heat, dehydration, pressure, and even radiation. Researchers at the University of North Carolina have found that ~ 1/6 of the entire genome of the Tardigrade species Hypsibius dujardini originated from other organisms, mainly bacteria and some plants and fungi. Before this study, the most abundant amount of foreign DNA in a single organism was half as much as the Tardigrade. These genes were obtained through horizontal gene transfer, which is the process of moving DNA from one organism, or the environment, to another by means of processes other than reproduction. Bacteria frequently use horizontal gene transfer to exchange plasmids that contain antibiotic resistance genes. The most likely way that horizontal gene transfer occurred for Tardigrades was that whenever they get rehydrated after becoming dessicated, their membranes are "leaky" which allows large amounts of DNA to enter. The Tardigrade's genome is degraded after dessication, so when it pieces back its genome during rehydration, the large DNA fragments that are "stolen" from the environment are randomly incorporated into the genome.These foreign genes haven't been fully characterized, but they are believed to be main contributors to the robust qualities of the Tardigrade. The authors of the study say that their results "suggest that organisms that survive extreme stresses might be predisposed to acquiring foreign genes." This is a neat idea and I'm interested to see what the applications of this finding will be.


Reference:

Almost 1/6 Of Tardigrade DNA Is Foreign

Evidence for extensive horizontal gene transfer from the draft genome of a tardigrade

Taste - it's all in your head

When we taste a food, whether it be sweet, salty, bitter, sour, or umami (savory), we think that our tongue is responsible for telling the brain what it is. Instead, researchers found that the brain is responsible for interpreting what the taste is based on which group of neurons the chemical signal is sent to. To put it more simply, if you eat a sweet food and the sweet neurons are suppressed, the sweet taste receptors in the tongue will still be activated, but the food will not taste "sweet" anymore. On the other hand, if the sweet receptors are activated and the others are suppressed, all foods will "taste" sweet.

To test this, researchers gave mice a drug to suppress either the sweet or bitter neurons. Then they gave the mice sweet and bitter foods. The mice that had the bitter neurons suppressed could only taste the sweet foods and vice versa. They also tested these neuron groups by activating the sweet or bitter neurons while the mice were drinking water. When the sweet neurons were activated during drinking, they "observed behavioral responses in the mice associated with sweet, such as impressively increased licking". When the mice were drinking water with the bitter neurons were activated, the mice started gagging and performing "taste-rejection" behaviors. On the bright side, once the drugs were flushed out of the mice's system, all of their "tastes" returned back to normal.

Imagine if we could make all the healthy foods "taste good" and unhealthy foods taste bitter, especially to those who want to change their eating habits. More often than not, I don't eat healthy foods because some of them activate my gag reflex for some reason (other times it's the cost factor that keeps me away, but that's a different story). If I could take a pill before I eat to make that problem go away, I might be more inclined to eat those foods. Also, if I know I have a problem with over-eating sweets, I could take a pill to activate my bitter neurons to deter me from eating too much sugar. This was an interesting study to learn about and I'm curious to see where they take it from here.

References:

Scientists turn tastes on and off by activating and silencing clusters of brain cells

Yueqing Peng, Sarah Gillis-Smith, Hao Jin, Dimitri Tränkner, Nicholas J. P. Ryba, Charles S. Zuker. Sweet and bitter taste in the brain of awake behaving animals. Nature, 2015; DOI: 10.1038/nature15763

Telomeres - the giver of life and death

Telomeres are extra chunks of DNA at the ends of chromosomes that protect important segments of DNA from being lost during cell replication and division. As a cell keeps replicating, the telomeres become shorter. Once the telomere is gone, the cell stops dividing and becomes senescent before it eventually dies. Telomeres can be extended by the enzyme telomerase, which results in cell immortality as long as the telomerase is still functioning. This enzyme is present in immortal cells such as germ cells and stem cells. Additionally, telomerase is over-expressed in cancer cells, which is one of the many reasons why they are able to replicate uncontrollably. 

Telomerase was only discovered within the past 50 years, so details about its structure, function, and expression, among others, is still being researched or recently found. For example, ATM kinase has been known to be involved in DNA repair, but now researchers found that it is also involved in the elongation of telomeres. Getting to know how each enzyme and other proteins are involved in this process could allow them to be manipulated, such as shutting down elongation in cancerous cells or stimulating telomere elongation in aging cells. However, there is a delicate balance between elongating telomeres for longer-life spans/anti-aging and keeping them at a controlled length so that the cells don't become cancerous and have the opposite effect (i.e., death).

Reference:
Another Telomere-Regulating Enzyme Found

Tetragametic Chimeras - a.k.a. "Twin Eaters"

As a follow up from last week's post, I thought I'd go into more detail about the phenomenon of chimeras, specifically tetragametic chimeras. Chimeras are organisms that contain cells that are genetically different from each other. As the name suggests, tetragametic chimeras form from the fusion of two separate eggs that have been fertilized by two different sperm. More simply put, it is the fusion of two non-identical twin embryos during early development. Chimerism can be easily seen in several non-human animal species, such as the well-known example of Venus the Cat (right). However, in humans it can be less obvious (an exception would be true hermaphrodites).





In chimeric humans, different cell lines have one of the sets of DNA. For example, liver cells may have the same DNA found in saliva, but not the same DNA in brain cells or gametes. A famous case study of this phenomenon was regarding Lydia Fairchild (click on name to see video of her story), who found out she was not genetically the biological mother of her three children when she filed for welfare, which requires the parents to prove that the kids are theirs. Since she failed the maternity test, she was charged with welfare fraud and almost lost the case until doctors decided to test her DNA from multiple cell lines, such as her blood, hair, saliva, and cervical cells. Only the cervical cells provided a match to her children. As in vitro fertilization becomes more common, tetragametic chimeras have become more abundant, due to the practice of implanting several embryos into the mother to increase the chance of pregnancy, which increases the probability that two fertilized eggs might fuse (Strain 1998). To prevent future failed paternity and maternity tests, children who are the product of in vitro fertilization should have multiple cell lines screened to see if they are chimeric.

References:
Lisa Strain, Ph.D., John C.S. Dean, F.R.C.P.(Edin.), Mark P.R. Hamilton, F.R.C.O.G., and David T. Bonthron, M.R.C.P. A True Hermaphrodite Chimera Resulting from Embryo Amalgamation after in Vitro Fertilization. N Engl J Med 1998; 338:166-169. January 15, 1998 DOI: 10.1056/NEJM199801153380305

WEIRD OR WHAT? -- TETRAGAMETIC CHIMERA

"THE RESULTS ARE IN - You are..... NOT the father!"

The world has seen many relationships end after the utterance of this sentence on the famous TV show, "Maury". As I was scrolling through Facebook the other day, I looked over at the "Now Trending" tab on the side and saw a link that said "DNA: Father Failed Paternity Test Due to ‘Chimeric’ Genes, Researchers Say", so I of course clicked on it. What followed was very interesting. A couple from Washington used a fertility clinic to help them have a child. The pregnancy and birth went well, but they later found out that the child's blood-type did not match either parent, so they decided to do a paternity test, which the father failed. This lead them to assume that the clinic might have swapped the sperm samples with an unknown donor.

Simply put, a paternity test is done by taking saliva or blood samples from the child, mother, and father(s) in question and comparing the alleles to each other. The child's alleles should have several matches to the mother's and father's, some matches to a non-parent family member, and fewer to none matches to a stranger/non-family member (if the child has no matches, they are probably adopted).


The failed paternity test then led them to do a full DNA test on the father's and child's DNA, after which they found that there was a 10% match, suggesting that he was actually the child's uncle, rather than father. These tests were done using DNA from blood and saliva samples, so doctors then tested his sperm, which contained the match to the child. This phenomenon is called chimerism, which is when a person has extra genes/DNA that were absorbed from an unborn/miscarried twin in the womb. This theory of the man being a chimera supports the uncle results since the DNA in his gametes is ultimately from his unborn brother. Weird, huh?

What if the unborn twin had been a girl? Would that mean that this man's gametes would be eggs, and therefore make him unfertile, or would his sperm contain female DNA that would guarantee that the only children he and his wife could have were girls? The news article I read only mentioned another case where the unborn twin was the same sex as the chimera, so it would be interesting to look into this possible scenario.

Mind Control

Researchers have developed a tiny brain implant that can remotely deliver therapeutic drugs or light pulses to treat certain neurological disorders. They were also able to control certain behaviors, such as turning around in circles. Watch the video below:

I'm not sure how comfortable I am with the idea that someone could inject drugs directly into my brain or stimulate it with an LED light, but the decrease in invasiveness may be appealing to some people. What do you think?

Malaria can be a cure for cancer?!?!

Malaria is bad, right?! Nobody wants malaria. On the other hand, cancer pretty much sucks too. Turns out, the malaria parasite, Plasmodium falciparum, has a protein involved in the parasite's invasive mechanism called VAR2CSA which binds to a specific sugar (Oncofetal chondroitin sulfate) thought to be found only in placental cells, which is why pregnant women have a higher risk for malarial infections. However, cancer cells have been found to also display this sugar. This wasn't too surprising, seeing as how both placental cells and tumor cells have rapid and uncontrollable growth.

Once researchers made this connection, they began developing a way to manipulate the VAR2CSA protein into a drug-delivering vehicle that is specific to tumor cells only so healthy cells are unaffected. In the very recent animal trials, tumors in mice infected with non-Hodgkin's lymphoma shrunk by 75% compared to untreated mice, 33% (2/6) of mice with prostate cancer went into remission, and over 83% (5/6) of mice with stage V breast cancer were completely cured. It will take a few more years to develop a system fully safe and efficient for human trials, but at least there is some hope!

References:

Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein

Malaria Protein Could Give Us A Broad Cancer Treatment

DNA - not as easy as GCAT

Almost everyone with a basic knowledge of biology knows that the four primary DNA nucleotides are guanine (G), cytosine (C), adenine (A), and thymine (T). In the 80's a fifth base, methylcytosine (mC), was found and from this discovery, methylation was shown to play a major role in epigenetic changes. However, over the last few years more bases have been discovered and also synthesized, so it is possible that the current DNA alphabet will expand rapidly in the near future.

Naturally or chemically modified bases:

• mA --> methyladenine (known to be in bacteria, but researchers are still trying to see if this exists in mammals)
• 5hmc --> 5-hydroxymethylcytosine
• 5fc --> 5-formylcytosine
• 5cc --> 5-carboxylcytosine

All of these bases can play a role in stem cell research, such as being able to reprogram adult cells into stem-like cells through demethylation. Also, they can be used to reactivate tumor suppressor genes that may have been silenced through methylation in tumor cells.


Engineered bases:

• "Z" --> 6-amino-5-nitro-2(1H)-pyridone
• "P" --> 2-amino-imidazo[1,2-a]-1,3,5-triazin-4(8H)one 

      These bases pair together and can form a double helix just like G-C and A-T pairs and provides the potential to build new proteins for medicinal purposes.


References:
New Nucleotides Identified in Human DNA
Sixth DNA base discovered?
Extra DNA Base Discovered
Structural Basis for a Six Nucleotide Genetic Alphabet

DNA Fingerprinting Using STRs

Genetic testing is an ever-expanding field for scientific and criminal investigations. DNA technology, such as the use of multiplex PCR to analyze short tandem repeats (STRs) – gene segments that are highly polymorphic and are abundant in the non-coding regions of the human genome – has become a new alternative to traditional methods such as southern blots using variable number tandem repeats (VNTRs). VNTRs are also comprised of repeating sequences, but are much longer per repeat (10-100 base pairs vs. 2-9 base pairs) and are generally not as conserved across generations compared to STRs, which makes familial testing more difficult.

The use of STRs for genotyping individuals is commonly known as “genetic fingerprinting” or "DNA profiling". Multiplex Polymerase Chain Reaction (PCR) kits are commercially available, allowing several STR locations (loci) to be amplified and characterized all in one reaction per sample versus several individual reactions of the same sample using regular PCR; this process is quicker and more efficient. The results include the allele patterns for each autosomal locus tested (numbers and locations vary between kits) as well as the Amelogenin locus, which gives the sex of the individual. The more loci you add, the more unique the profile becomes, which is why CODIS uses 13 loci plus the sex marker. Since the small nature of these markers allow them to be more resistant to mutations and degradation, this technique has become highly popular not only for crime scene analysis or paternity testing, but also in the identification of remains from highly traumatic events such as fires, explosions, and airplane crashes, amongst others.

To get a better break-down of this method, watch the video below:

An Age Old Question

You may be thinking of many different questions this could possibly be about, such as: "Which came first, the chicken or the egg?" - nope! Or, "Why did the chicken cross the road?" - try again! How about, "What is the meaning of life?" - wrong.

The correct answer is, "Are viruses alive?"!!

This has been very controversial in the scientific community for many, many years. The most commonly accepted answer is, no. The basic requirements for an entity to be considered "alive" are as follows: capability of homeostasis, being composed of one or more cells, presence of DNA and RNA, metabolic activity, ability to grow, adaptability, response to stimuli, and the ability to reproduce.

Based on these qualifications, viruses fall short. However, a group of scientists in Illinois disagree. Since one of the main arguments is that viruses are not able to survive outside of a host, this group argues that there are other living species that rely on a host to complete their life cycle, so technically without that host, the other organism would cease to live and/or reproduce.

Other supporting evidence these researchers are gathering and focusing on is the composition of a tree of life that includes viruses by tracking their evolutionary history through their protein folds. These folds give a virus its shape and hundreds of these folds have been found in both viruses and cells. Also, viruses have been able to adapt and become infectious to cells that had been previously resistant, which is said to be the "hallmark of parasitism." Only about 5% of the estimated population of viruses have been discovered and sequenced, so it is possible that the key to this question lies in that 95%!

Do you think this is enough to change your mind? If not, what evidence (if any) would satisfy your skepticism? Comment below!!

Sources:
http://www.sciencedaily.com/releases/2015/09/150925142658.htm
https://en.wikipedia.org/wiki/Life
http://www.biolegend.com/NewsLegend/091615blog/AreVirusesAlive2.png

The New Workhorse of Gene Editing - CRISPR/Cas9

So what is CRISPR/Cas9? (I don't know why, but to me the first part sounds like how some people like their bacon) CRISPR stands for "Clustered Regularly Interspaced Short Palindromic Repeats" - quite a mouthful, huh? - and Cas refers to any CRISPR-associated genes/proteins. CRISPR sequences originate from prokaryotes and are most abundantly found in archaea. These organisms use this mechanism as their "immune system" as it allows them to cut beneficial genes from outside DNA sources and incorporate them into their own genome or to just inactivate harmful DNA from invaders, such as viruses or other bacteria.

There are multiple Cas proteins, but Cas9 is the main one associated with gene editing and silencing. Different forms of this protein play various roles in the editing process; for example, one form can induce double-stranded DNA breaks, while another form may only be able to bind to the target DNA and control the expression of that gene. This system is only 3 years old so there is much more potential to be discovered!


More detailed explanations and more can be found at the following sites:

https://www.neb.com/tools-and-resources/feature-articles/crispr-cas9-and-targeted-genome-editing-a-new-era-in-molecular-biology

https://en.wikipedia.org/wiki/CRISPR


Hope you enjoyed it!
-Michelle

Cats aren't the only ones that play with balls of yarn

Ever seen a cat playing with a ball of yarn? If not, watch this adorable video (or watch it anyway for guaranteed grins and giggles). 

The kittens are super cute, but the ball usually gets destroyed and yarn goes everywhere. However, with scientific advances, the yarn ball can fight back! Well.... not against a cat, but how about cancer?! In a recent study, researchers have developed a highly effective way to introduce gene editing proteins into living cells using a nano-vesicle in the shape of a clew (a.k.a. a fancy name for a ball of yarn). This structure is completely made of DNA, so the cell can easily recognize it and take it in. Inside, it contains a CRISPR-Cas9 complex, which is responsible for the gene editing function. A single guide RNA (sgRNA) can be designed to target certain areas of the genome to let the complex know exactly which DNA segments to cleave before they can be corrected.

So basically, the tiny ball of yarn sneaks its way into a tumor cell, for example, makes its way into the nucleus like nothing is going on, searches the genome, and if/when the sgRNA finds a bad gene, then bam! it sends the CRISPR-Cas9 complex to chop up the bad portion and then put it back together the way it should be through normal DNA-repair pathways. This will hopefully allow the cell to regain its original function and stop displaying tumor cell properties, such as the ability to bypass cell-division checkpoints, mobilize itself, or even avoid apoptosis, which are necessary qualities for tumor cells to proliferate and eventually develop into a cancerous cell line. So the next time you see a ball of yarn, think of the endless possibilities!!

Until next time!
-Michelle

1. Wujin Sun, Wenyan Ji, Jordan M. Hall, Quanyin Hu, Chao Wang, Chase L. Beisel, Zhen Gu. Self-Assembled DNA Nanoclews for the Efficient Delivery of CRISPR-Cas9 for Genome Editing. Angewandte Chemie International Edition, 2015; DOI: 10.1002/anie.201506030

Not familiar with the CRISPR-Cas9 system? Come back next week for a quick explanation!