What are eye boogers?

Indy

Indy doing the “thinking man”

My dog Indy is a boxer mastiff mix.  We named him after the scene in Indiana Jones and the Last Crusade when Indiana’s dad, played by Sean Connery, was pointing out that Jones’ actual name was “Henry Jones Junior. We named the dog Indiana.”  So we named the dog Indiana too! He’s a huge hunk of a dog at 65 pounds, but it’s balanced out by him being sweet tempered and a total snuggle-bug. We rescued him nearly a year ago from Boxer Luv Rescue (support them, they are awesome!). He was found on the border of Arizona and Mexico with a skin condition (likely mange) and entropion in both eyes.  This entropion causes his the eyelid to roll inward and irritate the eye, so he had surgeries on both eyes before we got him to try to fix this problem.  the surgery didn’t fix it 100%, so we use some lubricating gel to help soothe his eye when it’s needed. The only way we know there’s something wrong with his eyes is that he wakes up every morning with enormous eye boogers!  I’m not talking about the normal crusties that you have in your eye and quickly pick away each morning (my family used to call them “sleepy seeds”).  I’m talking about globs and globs of gunk that I carefully wipe out every morning and sometimes again in the afternoon with a wet washcloth.

Because of my now intimate and frequent involvement with eye boogers, I started thinking about what these actually are, what they are made of, and why they are sometimes crusty, sometimes gunky and sometimes just plain disgusting. To answer these most important questions, I went and did some research!

Thanks to http://www.refreshbrand.com/dryeye/dry-item/tear-film for the image

Thanks to Refresh for the image

Let’s start by talking about what is in your eyes besides your eyeballs.  Your eyes are protected by the “tear film,” which is made up of an outer oily layer, a middle water layer, and an internal mucus layer.  This is actually really cool if you think about it. Imagine you have a cup of water with a thin layer of oil over it.  The oil will slow down evaporation of the water just like the oily layer of the tear film.  It will also prevent stuff from getting into the water. These are two of the tear film’s major jobs: keep the eye moist and remove debris, which occurs while blinking.  The oil also acts as a lubricant to make blinking your eyes easier.  The mucus layer, closest to the eye, also helps prevent debris from getting to the eye because it’s super sticky (think of it as the flypaper of the eye) and traps foreign particles so that they can be removed from the eye by tears. The tear film also helps make your vision clear by making the surface of the eye smooth it refracts light properly, and it protects against infection (because it contains antibacterial substances).

The official name for eye boogers is “rheum“.  More specifically, eye boogers are one type of rheum, which is the discharge that comes from the eyes, nose and mouth during sleep. This discharge is made up of mucus, oil, dead skin cells and other debris (like dust) – so in other words, the discharge is made up of that tear film that protects your eyes throughout the day. So why does it gunk up at night?  Because at night, you aren’t blinking and the rheum isn’t being washed away by your tears. Instead the rheum collects in the eye and crust/gunk up in the corner of the eye.

Why are eye boogers sometimes crusty and other times (like in Indy’s case) completely goopy?  The wetness or dryness of the eye boogers can be different depending on how much of the moisture has evaporated from the tear film.  So with Indy, his eyes have more discharge because of the eye irritation and this accumulates into a goopy mess because the water isn’t evaporating from the rheum when he sleeps.

Even though eye boogers change from night to night, there are medical reasons why you may have more or less eye boogers.  These changes in color or consistency could be an indication of a problem – such as dry eyes, an eye infection, a clogged tear duct, allergies or other eye irritation. So if your eyes are crusted shut or if your eye boogers are green, you can first tell your friends how eye boogers are made, and then get yourself to a doctor.

When I talked to my Mom about this post (she gets sneak previews because she’s my mom), her main question was whether dog eye boogers and people eye boogers are the same.  From some limited research, I found that dogs also have a tear film composed of the same layers the human’s have and has the same purpose.  Different parts of the dog eye anatomy create these layers compared to humans, but otherwise, it seems like it’s similar in concept. There are lots of articles about dog eye boogers (usually officially referred to as “eye discharge”) and many of the same problems, plus a few others, affect both dogs and people to cause abnormal eye boogers.  The same advice applies to people and dogs – if there’s more eye boogers or they start changing color, bring the dog to the vet to check it out.

Some of the other articles that have covered this extremely important topic:
Are yours crusty or wet? The truth behind eye boogers (ew)
Why do we get sleep in our eyes?
Where do eye boogers come from?
What are ‘eye crusties’ made of?

What are vaccines and how do they work?

Vaccines are a hot topic. Vaccines bring up lots of discussion, lots of false information, and a vitriolic passion rarely seen in matters of science and pseudoscience. I’m going to start my discussion about vaccines by explaining what they are and what they do. My second post will address some of the false information and controversy (with an added bonus of bringing in my lovely sister’s fabulous point of view as a mom of two!) My final post will answer a question I was asked about whether or not vaccinations are needed after a stem cell transplant.

Let’s talk about what immunizations do and how they do it.  Vaccines (aka immunizations) use biological agents to induce an immune response that protects you from that disease. The immunization itself could contain a weakened version of the disease-causing agent (like an inactivated poliovirus to vaccinate against polio), a non-human version of the disease (such as the cowpox virus to vaccinate against smallpox) or a small part of the disease-causing agent (for example, the toxin or a protein on the surface of the disease-causing agent).  The vaccine is injected into the body, but it isn’t strong enough or functional so it doesn’t cause the disease, but the body attacks the vaccine’s biological agent using immune cells and develops a “memory” of this infection.  This memory is made up of both antibodies and immune cells.  Antibodies are shaped like the letter Y and the top part of the Y functions like a puzzle piece that fits together with a complementary piece on the infectious agent (called an antigen).  When the anitbody encounters a matching puzzle piece it will bind to the infectious agent and kill it quickly before it can cause disease. Therefore, the effectiveness of a vaccines depends on how good the vaccine is at making a puzzle piece fits the antigen puzzle piece on the infectious agent.
antibodySo let’s have an example.  The flu vaccine contains small proteins from several flu strains that, when injected, stimulate the immune system to create antibodies against those flu strains.  When a person encounters the flu,for example because their neighbor has the flu and sneezed on them, the antibodies and immune memory that were created by the vaccination will attack and neutralize the flu virus before it can infect the cells and make you sick.  If the flu vaccine didn’t contain proteins that create puzzle piece antigens that bind to the most common flu strain in a particular year, the flu shot is less effective and more people will get the flu.

Vaccines have done amazing things.  They have eradicated smallpox, a deadly disease that had been around for over 12,000 years and killed 30-35% of people who were infected.  Eradicating this disease saves the lives of over 5 million people each year who would have been infected and died otherwise.  Polio, another crippling disease, has nearly been eradicated with only a few hundred cases in 2012 compared to over 350,000 in 1988. Common childhood diseases like measles and whooping cough have also been decreased considerable, saving millions of lives each year through vaccines.  They are truly a modern medical miracle!

Does the media sensationalize terrible science? Oh, yes.

The other day, I was drinking a glass of wine with a friend of mine, and she mentioned a story that she recently read in Scientific American called “Changing Our DNA Through Mind Control.”  She was excited to tell me how scientists had found that decreasing your stress can actually change your DNA! This was fascinating!  She was excited!  I was excited!  But being the scientist that I am, I wanted to understand what, how and why, so I needed more information. To gather this information, I looked at the original scientific article in the journal Cancer. (see here for my post on what a scientific article looks like).

om

Thank you Wikipedia for the image

The researchers had taken breast cancer patients and split them into two groups – one group went to mindful  meditation classes and the second group did not.  The scientists then took a sample of their DNA isolated from the patient’s blood and tested the length of their chromosome’s telomeres. To remind you, all people have 23 pairs of chromosomes in each and every cell. Telomeres are found at the ends of the chromosomes and protect the chromosomes from being damaged (essentially eaten away at from the ends by DNA-chomping proteins inside the cell).  A common comparison is to think of telomeres like the plastic bits at the end of shoelaces. The shorter the telomeres (or the shorter the plastic bit), the closer the chromosome (or the shoelace) is to being damaged.   In this study, the researchers found that the telomeres in cancer patients who went to meditation were longer than the patients that didn’t . Because of this, their DNA was better protected.  How incredible!

How unbelievable. Unbelievable for a few reasons:

  1. The researchers looked at the length of telomeres over a three month time span.  Telomeres shorten over a lifetime, so I wouldn’t expect to see a significant change over 3 months (whether sick, well, stressed, or not stressed).
  2. Because of this reasoning, I looked carefully at the data they presented in the paper.  None of it was statistically significant.  There is a trend that showed that patients that did not go to meditation were slightly, on average, a tiny bit lower than patients that went to mediation, but nothing that convinces me that what they are seeing is real,  In fact, even the paper’s authors said that if they wanted to have enough patients to get to statistical significance in the results, they would need to do a bigger study with more than double the number of participants.
  3. As a final nail in the coffin, in the psychological analysis comparing the mood of the meditating versus non-meditating patients, the researchers didn’t notice a change in stress or mood scores.  So even if there was a change in the DNA (which there isn’t), since their mood doesn’t change, a decrease in stress cannot be the cause of the telomere/DNA changes.
I’m not saying that mood doesn’t have the ability to affect your DNA – maybe it does.  I just don’t think that they showed it in this study.
chocolate

Thank you Wikipedia for the image

But I don’t want to harp on these researchers or this study. In fact, here’s another interesting example. A science journalist, Dr. John Bohannon, recently wrote a scientific article based on an actual study that they did studying people’s diet and how chocolate contributed to their weight loss. They found that eating chocolate once a day significantly increased weight loss!  The data was real, they published the results, and the media picked it up like wildfire.  It was published by news media around the world!!! Only problem – the conclusions they they drew were crap, and Dr. Bohannon published them with the intention of baiting the media.  In this case, there were too few participants, so they found something that was “statistically significant” in this group of people but wouldn’t necessarily pan out if there was a full, well-designed study. John Bohannon wrote a great blog post about this whole experiment and why this is the case.

So what’s the message here?  I think the first is that the media often looks for science that can create a striking, head-turning headline.  The problem is that when the conclusion is so cool, journalists don’t always read the original article or evaluate the data to make sure that this cool headline is supported by evidence in the publication.  To be fair, journalists may assume that since other scientists already reviewed the paper for scientific accuracy (a process called “peer review”) that it will be good to go.  But just because a stranger hands you a drink in a bar and says its okay, should you just believe them that it doesn’t contain Roofies?  I also don’t want to imply that all science journalism falls into this trap, but with ever shortening deadlines and competition for the “hot headline,” I can only imagine how appealing it is to take shortcuts.

To conclude, I actually have a problem in writing this post in that I don’t have a solution for you, my reader.  Unlike the friend I was having drinks with, you may not have a scientist at your beck and call to vet all news stories for scientific accuracy.  And as much as I hope that this blog is helping you to obtain your own PhD in biology, you won’t have all the tools you need to evaluate scientific articles on your own.  So maybe I will leave you with a tried an true saying “Don’t believe everything you read” or maybe “If it sounds too good to be true…” it might be.

I’m not the only person who has written about this topic.  If you’re interesting in reading more, check out this article from NPR, numerous articles from Ben Goldacre about how science is misrepresented in the media compiled on Bad Science, and a different point of view, an article published in Salon about how just because someone is a scientist doesn’t mean that they are an expert (especially if they are on Fox News).

Why is the specificity of a biomarker important? PSA for prostate cancer as an example.

I’ve described what biomakers are here and how they are discovered here. I’ve spent so much time discussing biomarkers because this is one of the aspects of personalized medicine that you may have already encountered in your doctor’s office or will encounter soon.  Similar to how we understand risk, it’s important to understand biomarkers because many healthcare decisions will be based on the results of tests that look at the presence, absence, or quantity of biomarkers.

So how do you know what the results of a biomarker test mean or whether or not a biomarker is good or not?  Scientists have created two measurements that can quickly tell you how good a biomarker test is: sensitivity and specificity.  Before we talk about what those two measurements measure, let’s first talk about the different scenarios for a patient after getting the result of a test using a biomarker.

  1. The test is positive and the patient has the disease. This is a good scenario because then the patient can move forward with the appropriate treatment.
  2. The test is positive but the patient doesn’t have the disease.  This is what we call a “false positive” because the test is incorrectly showing up as positive.  This can cause huge issues because a patient will receive a diagnosis, follow-up tests or treatment even though they don’t have a disease.
  3. The test is negative and the patient doesn’t have the disease.  Again, this is a good scenario because the patient is a-okay.
  4. The test is negative but the patient has the disease.  This is a “false negative” because the test is falsely showing that the patient doesn’t have a disease when they actually do.  This can also cause issues because then a patient won’t be treated even though they should be.

sensitivity_specificitySensitivity and specificity measure the best case scenarios – sensitivity measures when the test is positive and the patient has a disease and specificity measures when the test is negative and the person doesn’t have a disease.  The ideal test has 100% sensitivity (all sick people are tested as being sick) and 100% specificity (all healthy people have a negative test).  But this ideal situation is difficult to achieve.  Let’s use Prostate Specific Antigen (PSA) as a biomarker test for prostate cancer as an example.

There are 241,740 new cases of prostate cancer each year, and it is the most common malignancy in men (29% of all male cancers).  PSA levels are screened in men over 50 for increased expression and over $3 billion per year is spent for this screening.   What is PSA? It’s a protein produced by the prostate gland and can be elevated in men with prostate cancer, which is why it has been used as a biomarker for prostate cancer.  However, PSA may also be elevated in men with other conditions such as prostatitis (inflammation of the prostate), benign prostatic hyperplasia (enlargement of the prostate), or urinary tract infections.  Because of this, the PSA test is highly susceptible to false positives and false negatives.  Typically PSA greater than 4 ng/mL (this means that there is 4 nanograms of PSA protein in 1 milliliter of urine) is considered a positive test result for prostate cancer.  The sensitivity at this level is 21%, which means 21% of patients that have prostate cancer have PSA levels  greater than 4 ng/mL.  Specificity of the test is 91%, which means that 91% of patients who test negative do not have prostate cancer. This is good – there aren’t many patients who don’t have prostate having follow-up test or biopsy because of a false positive (because of the high specificity).

Let’s see what happens if a lower concentration of PSA are used as a cut off to try to detect more patients with cancer.  If you look at patients with greater than 1.1 ng/mL, the sensitivity increases significantly to 83%, which means that more people with cancer are being detected (great news!).  The trade off is a specificity of 39%, which means that a huge number of patients will be incorrectly diagnosed as having cancer (high false positives).  This will result in follow-up tests and biopsies.  The effect of these tests and biopsies are both psychological (thinking you have cancer when you don’t) and physical (an increased risk of complications and side effects caused by the biopsy).

psa test

So is PSA a good test or a bad test?  For the patients who have received a positive PSA test and have aggressive prostate cancer, this test saves lives.  However,because this is a common screening test, it does cost a lot of money.  Because the sensitivity of the test at higher PSA concentrations is so low, some cancers get missed.  And if the cut off is decreased to catch more of these cancers, there’s a much higher number of false positives in men who do not have prostate cancer resulting in costly, stressful test that may have added complications.

What’s the solution?  In the case of PSA, doctors have started measuring PSA levels over time.  Increases in PSA levels over time are found more often in men with prostate cancer.  PSA also exists in a few different forms. PSA can either be attached to other molecules or not.  The form that isn’t bound to other molecules is called “free-PSA” and scientists have found that the amount of free-PSA compared to the total amount of PSA is reduced in men with prostate cancer.  These improvements have decreased false negatives and false positives, making it a much better test.

Overall, biomarkers have the potential to revolutionize medicine, and in so many cases they already have.  But for you as a patient, understanding the challenges and pitfalls of these tests will help you be a more empowered patient with the knowledge to ask key questions when you receive the results from one of these new tests.

 

What is a biomarker? A cornerstone of personalized medicine.

What is a biomarker? Biomarkers are biological measures of health or disease and are a cornerstone for personalized medicine.Historically, diagnosing a disease was based on symptoms. This reminds me of a joke.  A patient goes to see the doctor and tells him “Doctor, I hurt everywhere.” The patients touches his head “I hurt here”, he touches his arm “I hurt here”, he touches his stomach “I hurt here” and on and on.  The doctor looks at him and says “I know what’s wrong with you!  You have a broken finger!”

No one wants to be diagnosed or misdiagnosed with a broken finger. This isn’t to say understanding symptoms and using this information to contribute to a diagnosis isn’t important.  But what if…
…symptoms don’t lead to an obvious diagnosis?
…two patients have the same symptoms, but different diseases?
…two patients have the same disease, but different causes – either the root cause is different or they both have lung cancer but the genetic mutations in each cancer is different.  In this case different treatments would be are needed.
…two patients have different diseases, but similar causes – maybe they both have the same genetic mutation in two different kinds of cancer –  so the same treatment can be used?

biomarkerThis is where biomarkers come in.  Biomarkers are things in the body that can be measured to give us information about a disease or other condition.  Biomarkers can be a variety of things including

  • Imaging methods
  • Genes (presence or absence)
  • Specific gene mutations
  • Proteins or antibodies
  • Metabolites
  • Microbes?

And these things can be measured to in some way indicate if the person is healthy or has a disease.  Other biomarkers may be used to detect a disease earlier than when the patient is showing symptoms.  Detecting a disease early may allow the patient to change a behavior to decrease the likelihood of developing the disease or to start treating a patient earlier when it is easier to successfully treat a disease. Biomarkers may also be used to determine the severity of a disease or whether or not the disease is progressing.

biomarker_types
Some biomarkers that you may be familiar with are cholesterol, temperature, and blood pressure.  There are a number of biomarkers for pregnancy. Home pregnancy tests look for the presence of the protein beta human chorionic gonadotropin (also called beta-HCG) in the urine.  This protein biomarker is in the blood after the zygote implants 6-12 days after fertilization.  Other biomarkers such as serum creatinine and liver enzymes are markers for kidney and liver function, respectively.

So what makes a good biomarker?  First, it needs to be different if the patients has a disease.  For example, higher than normal blood glucose levels may indicate that a patient has diabetes and these levels of blood glucose would not be found in a patient who didn’t have diabetes.  Second, the biomarker would have to correlate with the outcome.  What this means is that as the patient’s condition changes, the biomarker would also change. In the case of the patient with high blood glucose and diabetes, when the patient starts regulating their diet or taking insulin, the blood glucose levels will go down.  Third, biomarkers should be easy to access, and one of the main reasons for this is so that testing for the biomarkers isn’t too expensive.  Blood is a common location for biomarkers, including in our example of blood glucose levels.  Finally, biomarkers should be consistent.  It wouldn’t be useful to have a biomarker that changes based on whether it’s noon or midnight.  It needs to be dependent on the health of the patient.

Biomarkers are a cornerstone of personalized medicine because they allow clinicians to use symptoms along with measurable and quantifiable factors in the body (the biomarkers) to diagnose, track, and treat disease. Learn more about biomarkers in this YouTube video

What are all the “-omes” in science?

If you’re into yoga, you may be very familiar with “OM” or if you’re an electrician with “ohms”, but in science, we use “-ome” in a very different way.  To start off, let’s give a silly example: the studentome (which I’m fairly sure does not actually exist).  This would be the study of all “students” in a certain place.  Maybe we’re interested in all of the students in a particular high school or college, and they can be categorized and better understood by looking at the distribution of their ages, their heights, their grade level, their clothing style, etc.  The studentome would be different in an inner city school compared to a private Catholic school, and understanding these differences could help to improve or change aspects of the studentome in a certain place. The study of the studentome, would be called studentomics.

So what does this “-ome” mean? In Greek: “-ome” means “all” or “complete”. So whenever scientists put “-ome” at the end of a word, they are talking about all of something (like with the “studentome” all of the students), and in biology this usually is referring to all of something in an organism or a particular cell type.  It’s not clear when scientists started using words ending in “-ome”, though the word biome was coined in the early 1900s.  The modern usage likely started in the early 1990s as technologies, like computers and DNA sequencing, allowed scientists to study all of something in an organism with more ease.  A derivative of the “-ome” is “-omics”, which is the study of all of something in an organism or a cell.  This terminology is so common, there is even a wiki dedicated to “-omes” and “-omics” here.

Let’s explore some of the common “-omes” (you can find a more comprehensive list of scientific “-omes” here).

  • Genome: The most famous “ome” is the genome. The genome refers to all of the DNA in an organism.  In humans, this includes all 23 pairs of chromosomes (number 1-22 and the two sex chromosome, XX if you are female and XY if you are male). Scientists study the genome to understand the genetic blueprint of DNA because DNA codes for proteins, which are the functional machines that do everything in a cell.
  • Transcriptome: For DNA to make a protein, the DNA needs to be “transcribed” in RNA first (read more details about this process here).  All of the RNA in a cell is called a transcriptome.  Scientists study the transcriptome because not all DNA is “turned on” to make proteins in every cell.  This helps explain why certain cells look different (skin cells look different than eye cells) and have a different function (skin cells provide a barrier from the environment and specialized eye cells allow you to see).
  • Proteome: And this brings us to the proteome, which is all of the proteins in a cell or organism.  Since proteins are what’s actually doing stuff in a cells, by understanding what proteins are present in certain cells, scientists are able to better understand how those cells function. And in the case when there are problems, for example in cancer cells, it can help understand why there is a problem and possible ways to fix it.

omes

  • Interactome: Proteins interact with one another in a variety of ways.  The interactome maps all of these interactions.  The interactome is also different in different cell types because the proteins expressed are different in different cell types, so there are many interactomes
  • Metabolome: Even though proteins are the machinery in a cell, there are lots of other small molecules and chemicals called metabolites.  For example, glucose is a metabolite that is broken down to produce energy.  All of the metabolites in an organism are called the Metabolome.

And there are hundreds more of these “-omes”!  This “omeome” (originally and jokingly coined here) has even seeped into more popular culture.  For example, the Facebookome, described as “The totality of facebook social network connections and nodes information such as people’s names, relationships, and multimedia contents.”  Although it may seem to be an unnecessary wordy trend, these “-omes” and “-omics” are necessary for scientists to better understand health and disease.

 

 

What happens when chromosomes rearrange? Sometimes cancer.

There are so many different kinds of genetic mutations.  So far, we’ve only discussed small single nucleotide changes and insertions and deletions.  But entire pieces of chromosomes can also be rearranged in what’s called a translocation. The prefix “trans” shows up a lot in science.  It comes from Latin and means “across” or “on the opposite side”.  “location” is physically talking about the chromosomal location.  So “translocation” mean s pieces of chromosomes moving to another location.

translocation

You can think of it as two different pieces of DNA that aren’t usually right next to each other, being put next to each other. Kind of like a centaur – the top of a human attached to the bottom of the horse – a human/horse translocation.  Of course, in the case of chromosome, genes or regulatory pieces of DNA are moved next to each other, and although it may not seem nearly as dramatic as a centaur, the effects can be just as surprising.

philadelphia chromosomeOne example of a translocation that has dramatic consequences is the translocation that causes the blood cancer Chronic Myelogenous Leukemia (abbreviated as CML).  In this case, part of Chromosome 9 and part of Chromosome 22 break off and swap.  So now, Chromosome 9 has part of chromosome 22 attached, and vice versa.  The part of chromosome 22 and the broken off part of chromosome 9 are called the Philadelphia chromosome, and this is what causes the leukemia.

But how?  We  imagine that Chromosome 9 and Chromosome 22 are both train tracks.  On those train tracks are trains that can either be going or not going depending on the upstream signals.  On Chromosome 22 there is a green signal that is stuck at green so the train is always going.  On Chromosome 9, there is a more sensitive signal – some times it’s green, but most of the time it’s red so the train isn’t going.

train_anaolgy

What happens now is that there is a switch (or a translocation) that attaches the Chromosome 9 and 22 train tracks together.   But when it does this, the green signal from Chromosome track 22 is telling the train on the chromosome 9 track to go – even though it usually doesn’t always go.  This is nearly exactly what happens in the case of the Philadelphia chromosome, except the trains are genes that are making protein (if the signal is green) or are not made into protein (if the signal is red). The signals are parts of DNA that regulate the “expression” of the gene (in other words, whether or not the gene makes the protein).

train_analogy_switch

In the case of the translocation in CML, what happens is a gene of Chromosome 22, called BCR is attached to part of the Abl gene on chromosome 9.  In this configuration, the BCR-Abl fusion gene makes a protein that is always “on”.   What does this protein do?  Essentially, it tells the blood cells to keep growing and dividing.  This makes too many blood cells and causes leukemia.

There are many different chromosomal translocations that cause a number of different diseases, but what they have in common is either creating a protein that is always on or changing the upstream signal that tells a gene to make more protein.  Most of the time, this results in signalling the cell to keep growing and dividing, which is why translocations are often associated as a cause of cancer.

How do mutations change proteins?

We’ve talked about mutations and how they can be good, bad or neutral, but how does that work exactly?  This is the nitty gritty. Remember back to how DNA is transcribed into messenger RNA which is then translated into the protein?  This is based on a three letter code – where each 3 letters of the RNA makes on amino acid. (If you’re interested in knowing how 4 nucleotides, which have 64 possible combinations makes only 20 amino acids, see my Answers page). If you change one of these amino acids a number of things can happen.

To make it easier, let’s pretend that these codons make the sentence “DNA HAS ALL YOU CAN ASK FOR” (see the picture below).  You may change one letter and it doesn’t change the meaning of the sentence (or the function of the protein) at all, making it a “silent” mutation. You may change one letter and it does change the meaning, but maybe not significantly – this is a missense mutation.  You may have a mutation that stops the sentence early – this would make a protein that is shorter than it’s supposed to be and probably will cause the protein to function improperly.  This is a nonsense mutation. Finally, you may add or remove one or many nucleotides which shifts the letter of the sentence so that they no longer make any sense.  These frameshift mutations also will affect the protein, and likely not in a good way.

protein_mutationsNow you can see how small changes may or may not affect the protein.    It’s interesting because it helps really explain how ONE nucleotide change can affect a protein and cause disease.  Also, if you think about the effect one nucelotide change can have, it helps us understand how finding and understanding these changes can be important for diagnosing disease.

 

Remind me how to make a protein?

You JUST HEARD about the central dogma last week, but it’s so important, that I think it’s worth a reminder – and the best kind of reminder is one in a video.

I also think it’s important to point out that there are a lot of details involved in the processes of transcription and translation.  And I don’t say this to make you feel badly that you don’t know the details, but rather to point out that these different steps all provide the cell with the opportunity to fine tune to protein production machine.  Back to our steering wheel analogy – you can take away the blueprint for part of the day so that the person can’t make steering wheels.  In this case, it would mean that something is making the DNA unavailable for transcription.  Or you could tell the person making the steering wheels to go on break.  This would be like getting rid of the mRNA.  Or you could take away some of the pieces needed to make the steering wheel, which would be like decreasing the production of an amino acid.  All of these scenarios happen!

I just want you to start thinking about how these steps can be “regulated” because then when we start talking about “deregulation” (meaning, when things aren’t regulated properly), you’ll understand that there can be many ways for this to happen.

transcription-translation

How does a gene make a protein? Introducing RNA!

Genes are pieces of DNA that code for a protein.  That sounds great…but how does it do this? DNA is made out of nucleotides (A, T, C, and G) and proteins are made out of amino acids.  To “crack the code” and transform the DNA code into the protein code, you need an intermediary.  That’s a molecule called RNA!  messenger RNA  (or mRNA, for short) to be precise, because it is the message that communicates the information from the DNA to the protein.

Let’s revisit our car blueprint analogy to discuss the role of mRNA.  If DNA is the blueprint for the steering wheel, and the protein is the steering wheel, mRNA is the person in the middle who reads the blueprint and builds the steering wheel.

gene_mRNA_protein

So let’s see how this actually works.  The first step is to understand what RNA is actually made out of. DNA stands for DeoxyriboNucleic Acid and RNA stands for RiboNucleic Acid, and if they sound like they are related, you are correct. Here are the three main differences

  1. DNA is double-stranded and RNA is single stranded (see the photo here)
  2. DNA is made from A, T, C, and G and RNA uses A, (standing for uracil), C, and G
  3. In DNA, A always matches with T, whereas with RNA, A always matched with U

Because they are made up of similar components, the cell can copy the code from the DNA into the single-stranded mRNA molecule.  Also because these two molecules are related, this process is call transcription – like what you would do when copying the words in a book from one place (DNA) to another (mRNA).

The mRNA is then what codes for the protein.  It does this just like you would expect any code to – using a key.  In this case, each set of 3 nucleotides codes for an amino acid.  The cells have machinery (called a ribosome) that “reads” the mRNA strand.  The combination of “ATG” always tells the ribosome to START making a protein.  It then reads the three digit code, adding the appropriate amino acids along the way, until it reads one of the three codons that tells the ribosome to STOP making protein.  At this point, the protein can fold up to make the 3D structure so it will function.  Because this process takes nucleotides and codes them into amino acids (a totally different molecule), this process is called translation.  Just like translating a book from English into French, this process translates mRNA into a protein.

translation

 

Wow what a lot to take in! This process from DNA (the gene) to mRNA to protein is called the “central dogma” of molecular biology.  This process was originally described in 1956 by Francis Crick (the same guy who along with Watson discovered the structure of DNA).  Why is it called this? Probably because when it was described, they realized that this was a fundamental process for all life.  It’s also important for us to know for so many reasons.  If you know that DNA codes for RNA which codes for protein, any changes in this process can result in a protein that isn’t quite right.  What if you have change the code of the DNA?  This will change the protein!  What if you change the amount of the mRNA? You will change the amount of protein!  And what can this do?  Cause problems in your cell that cause disease!

transcription-translation