Five Ways for You to Participate in Science – Citizen Science

Bunsen_burner

The Bunsen burner I didn’t have. Thanks Wikipedia for the image

I had a chemistry set growing up.  It was small with tiny white bottles holding dry chemicals that sat perfectly on the four tiny shelves of an orange plastic rack.  My dad would let me use the workbench in the basement to do experiments – entirely unsupervised!! You might expect that I did really interesting chemical reactions, and this formative experience helped me to develop into the curious scientist that I am today. Completely wrong.  I remember following the instructions, mixing the chemicals, and then getting stuck because I didn’t have a Bunsen burner.  So many chemical reactions rely on heat, and the green candle stuck to the white plastic top of an aerosol hairspray can wasn’t going to cut it.

My main options for doing science as a kid revolved my failed chemistry experiments, my tiny microscope and slides, and a butterfly net that never netted a single butterfly (not for lack for trying).  However, today with computers (that’s right – no computer growing up – that’s how old I am!) there are hundreds if not thousands of ways for people to get involved in science, without having to invest in a Bunsen burner. This citizen science movement, relies on amateur or nonprofessional scientists crowd-sourcing scientific experiments. I’m talking large scale experiments run by grant-funded university-based scientists that have the possibility of really affecting how we understand the world around us. One example you may have heard about is the now defunct Search for Extraterrestrial Intelligence (SETI) which used people sitting at their computers to analyze radio waves looking for patterns that may be signed of extraterrestrial intelligence. They didn’t find anything, but it doesn’t mean that they wouldn’t have if the program had continued!

Here are five ways that you can become involved in science from where you’re sitting right now!

americangut1. American Gut: Learn about yours (or your dog’s) microbiome

For $99 and a sample of your poop, you will become a participant in the American Gut project. After providing a sample, the scientists will sequence the bacterial DNA to identify all of the bacterial genomes that are present in your gut.  This study already has over 4,000 participants and aims to better understand all of the bacteria that covers and is inside your body – called your microbiome – and to see how the microbiome differs or is similar between different people or between healthy people versus those who may be sick. The famous food writer Michael Pollan wrote about his experience participating this the American Gut project in the New York Times.  They are also looking at dogs and how microbiota are shared with family members, including our pets!

2. Foldit: solve puzzles for sciencefoldit

Puzzles can be infuriating, but at least they have a point to them when you get involved in the Foldit project.  Proteins are the building blocks of life.  Made out of long strings of amino acids, these strings are intricately folded in your cells to make specific 3D shapes that allow them to do their job (like break down glucose to make energy for the cell).  Foldit has you fold structures of selected proteins using tools provided in the game or ones that you create yourself.  These solutions help scientists to better predict how proteins may fold and work in nature.  Over 240,000 people have registered and 57,000 participants were credited in a 2010 publication in Nature for their help in understanding protein structure.  Read more about some of the results here.

3. EyeWire: Mapping the BrainEyeWire-Logo

The FAQs on the EyeWire website are fascinating because as they tell you that there are an estimated 84 billion neurons in the brain, they also insist that we can help map them and their connections. After a brief, easy training, you’re off the the races, working with other people to map the 3D images of neurons in the rat retina.  You win points, there are competitions, and a “happy hour” every Friday night. The goal is to help neuroscientists better understand how neurons connect to one another (the connectome).

4. Personal Genome Project: Understanding pgpyour DNA

The goal of the Personal Genome Project is to create a public database of health, genome and trait data that researchers can then use to better understand how your DNA affects your traits and your health. This project recruits subjects through their website and asks detailed medical and health questions.  Although they aren’t currently collecting samples for DNA sequencing because of lack of funding, they have already sequenced the genomes of over 3,500 participants. The ultimate goal is having public information on over 100,000 people for scientists to use.

mindcrowd5. MindCrowd: Studying memory to understand Alzheimer’s Disease

Alzheimer’s Disease is a disease of the brain and one of the first and most apparently symptoms is memory loss.  MindCrowd wants to start understanding Alzheimer’s disease by first understanding the differences in memory in the normal human brain.  It’s a quick 10 minute test – I took it and it was fun!  They are recruiting an ambitious 1 million people to take this test so that they have a huge set of data to understand normal memory.

This is a randomly selected list based on what I’m interested in and things that I’ve participate in, but you can find a much longer list of projects you can participate in on the Scientific American website or through Wikipedia.  Also, if you’re interested in learning more about the kind of science that people are doing in their own homes, the NY Times wrote an interesting article: Home Labs on the Rise for the Fun of Science.  If decide to try one out, share which one in the comments and what you think!

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 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

What is a protein?

I keep mentioning proteins.  When I use this word, are you thinking of steak? or eggs? or protein shakes?  I am not talking about nutritional protein (though steak and eggs and protein shakes do all have protein in them), but rather the molecules in a cell that perform a ton of different functions in the cells.  Before we talk about what proteins are made of, let’s take a minute to think about what proteins do. They do a lot.  Proteins are how the cells of your body stay connected together, why and how you are able to digest food, why you are able to fend off disease, why you’re able to build up muscle and why you have energy.

protein_function

But what ARE proteins you ask?  Remember how DNA is made from a macromolecule called a nucleotide? Proteins are made from a macromolecule called an amino acid.  There are 20 different amino acids that each have different sizes and properties.  Some are hydrophobic (meaning they dislike water – like oil) some are hydrophilic (they are attracted like water – like wine).  Some are acidic (like lemon juice) or basic (like soap).  On average, a human protein has 500 of these amino acids strung together in a row, though some can be as small as just a few amino acids whereas the biggest protein called titin is 34,350 amino acids long.

Protein-structureIf you represent proteins as a string of amino acids, this is called their primary structure.  If this is all that proteins were, they wouldn’t do anything at all in the cell. Proteins need STRUCTURE to function.  It’s like rolling out a string of clay.  Until you coil the clay into the shape of a cup or a pot or a vase, it doesn’t have a function.

So what shapes do proteins make?  the two shapes are a sheet and a helix.  These sound exactly like you imagine them to look like.  The beta sheet is a flat piece of protein and the alpha helix looks like a spiral staircase.  However even at this secondary structure, the protein isn’t functional.  It needs to coil up even more into the tertiary structure, making a functional protein.

GFPWe can actually determine the shape of proteins in the same way that the double helix of DNA was determined : X-ray crystallography. Here is an example of what a protein looks like at the atomic level.  The flat parts are the beta sheets and that one tiny blue coil in the middle is an alpha helix.  This structure is of the GFP protein we talked about in a previous post.  So to bring it back to what proteins are made of, depending on the number, and properties of the amino acids in a protein, the protein will have a different structure and therefore will have a different function.

Here are some examples of proteins whose shape helps define its function

  • Cellular channels.  The size and shape of these proteins determines if large or small molecules can be let in and whether or not a key is needed to “unlock” the protein to open up the channel.  As an analogy, think about connecting two rooms to one another.  You have choices – you can choose to connect them with a door, which is much bigger and can let larger items through, or you can put in a window, which will let smaller items though. And either can be unlocked or locked.
  • Enzymes are another type of protein that often function by binding to another molecule or protein and doing something to it (for example, cutting it, in the case of digestion).  The shape of the protein will determine what it can bind to and what type of activity it can have.
  • And then there are structural proteins, like actin, that are long and stringy and help cells keep their shape, as you can see in the images below.

actin

When you think about proteins, just remember that depending on what they look like, they will do different things.  And if the shape of a protein is changed (say, by changing the DNA blueprint) the protein may not function as intended and could result in disease.

 

What is a gene and what does it do?

Genome – it has the word “gene” built into it. But what exactly is a gene? You may remember that the genome is made up of DNA, long strings of bases called A, T, C, and G.  There are certain strings of bases, called a genes, that code for proteins, and proteins are the molecules that do all the stuff in your cells.

Perfectly clear, right?  Of course not, so let’s start with an analogy.  Let’s imagine that one chromosome is a chapter of a book, but the book is written in such a way that the sentences with meaning are mixed in with random letters.  All of the letters are part of the English alphabet, but some of them are written in such a way that they make sense and have meaning – like the sentences written in red below. This is just like your DNA.  Some of the DNA makes readable sentences (genes) and other DNA in between these genes doesn’t (this used to be called junk DNA, but now we know better – more on that later!).
gene_analogy

Each of these genes makes a protein (the how of this is a topic for another post).  Let’s give a few examples of genes and proteins that you may be familiar with.  Insulin is a protein that is coded for by the insulin gene. Insulin is important in regulating blood sugar, and people with diabetes often need to inject the insulin protein to help regulate blood sugar.  Another example is the lactase gene.  This gene codes for a protein that makes the enzyme that breaks down lactose.  A decrease in the amount (also known as the “expression”) of the lactase gene is what causes lactose intolerance in adults.

An analogy that is used all of the time is to think of DNA as a blueprint for something – let’s say a car.  Each gene is a blueprint for a different part of the car – a steering wheel, a brake, or a headlight and the protein that each of these individual blueprints make is the steering wheel, brake or headlight itself.  The genome is all of the blueprints put together to make the entire car.  So what does this mean to you?  Imagine if the blueprint for the brake was a little wrong and the brake on your car didn’t work quite right…the car won’t exactly function as intended. It’s the same with genes.  If the gene isn’t quite right, it can make a protein that isn’t quite right, and this can cause the body to not function quite right (causing disease).

gene_protein

And just in case you’re sitting there and still thinking about blueprints and steering wheels and book chapters and codes, let’s summarize how the Genome, DNA, genes, and proteins are all connected in this image here:
dna_and_genes

 

Why does everyone, including me, like astronomy so much? OR – how I became a biologist.

Photo Feb 17, 6 57 16 PMI LOVED SPACE.  I loved space so much that in the sixth grade I spent most of my time at recess – without shame – with a friend planning on how to create a tractor beam (for those who aren’t complete geeks, that’s the force in Star Trek that allowed the Enterprise to latch on to other spaceships).  Our solution – a very big, long rope. Completely ignoring my fear of heights or adventure rides, I was convinced that I was going to be the female Jean-Luc Picard.  And as everyone else wrote in their sixth grade yearbooks how they wanted to be a teacher, doctor or lawyer, I wanted to be an aerospace engineer (and I honestly cannot believe that I’m showing the proof with my sixth grade yearbook photo).

"Aequorea victoria" by Mnolf - Photo taken in the Monterey Bay Aquarium, CA, USA. Licensed under CC BY-SA 3.0 via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Aequorea_victoria.jpg#mediaviewer/File:Aequorea_victoria.jpg

“Aequorea victoria” by Mnolf – Photo taken in the Monterey Bay Aquarium, CA, USA. Licensed under CC BY-SA 3.0 via Wikimedia Commons

With this deep-seeded love of astronomy, you may be asking yourself how I became a biologist?  In my senior year of high school, I attended a Boston University Medical Center program called City Lab.  This was a six week program that my mom drove my friend Missy and me to (an hour each way in rush hour traffic) so that we could do a lab experiment.  Each week, we spent several hours in the Boston University lab doing different parts of the experiment I describe below.

gfprabbitThe goal of this experiment was to take a piece of DNA that coded for the green fluorescent protein (also known as GFP) and put it into a piece of DNA that could make bacteria glow green.  We haven’t talked in detail about genes or protein expression yet, so I’ll stick to the basics. GFP is from a jellyfish called aequorea victoria, and it’s what makes the jellyfish glow green (see above).  A scientist isolated this one gene, and if transferred properly into another organism, it can make that organism glow green.  And yes, people have tried this.  People have created GFP rabbits and mice and…NO, NOT PEOPLE.  Why not?  Well, first, because it’s highly unethical to do genetic engineering in people for no clinical reason (and having glowing eyebrows will not cure any disease).  Also it’s very difficult to manipulate the DNA in humans for a variety of reasons that we will discuss when talking about gene therapy.

So, at City Lab our job was to cut the GFP gene using restriction enzymes (which are essentially DNA gpfbacteriascissors that cut DNA in a specific place) and then insert the GFP gene into another piece of DNA using ligase (essentially, DNA glue).  This  new piece of DNA (called a bacterial expression vector) makes the GFP protein in bacteria cells.  When the GFP protein is expressed in bacterial cells, the bacteria glow green (like the picture to the right).  It was easy to figure out if your six weeks of effort was worth it if your bacteria glowed green.

OUR EXPERIMENT WAS THE ONLY ONE THAT WORKED. Not only had we understood how a piece of DNA worked, moved it from one place to another, but we then were able to get it to do something in a bacterial cell.  At the time, I didn’t realize that this was what scientists called “recombinant DNA technology”.  I didn’t know that this was used all of the time in the laboratory as a foundation of molecular biology studies.  I had no idea that someday I would be managing a facility that stored hundreds of thousands of these pieces of DNA to help researchers worldwide with their experiments.  I only knew the thrill of “discovery” and I wanted more.

That’s how I became a biologist #tbt