Happy Sunday, Superheroes. Is everybody having a wicked weekend? My morning started EARLY today.
At this point you may be asking yourself: “Why did this oddball wake up at four in the morning to go run nine miles in the rain?”
The reason I decided to imitate a distance running Dracula this morning is because I had a plane to catch at 7:42 am. I finished my run, shed my spandex, put on compression socks, grabbed some oats in a jar that I prepared last night, and set off for SeaTac.
This week I am attending a conference at the Eaglewood Resort and Spa in Itasca, Illinois. The conference is called “Dynamic DNA Structures in Biology.” I could not be more excited for the week ahead. If it’s not abundantly clear, I’m more than passing fond of that magical macromolecule responsible for storing genetic information: the divine double helix, DNA.
My job is to study how Bacillus subtilis copies its DNA, and the problems that can happen when my favorite bacteria is replicating its genome. Specifically I am interested in what happens when the molecular machines responsible for copy the DNA run into the protein complexes that transcribe DNA into RNA. Here’s a brief recap of basic bio, if those terms seem unfamiliar and scary to you. I promise I’ll be gentle, and include some nice soothing images.
Every living thing on Earth is made out of cells (viruses aren’t made out of cells, and therefore viruses aren’t technically alive…we could argue philosophy taxonomy, and semantics about what is “life” all day, but I don’t want to…and don’t get me started on prions). Cells are bags made out of fats and carbs that are full of a molecular soup made out of nucleic acids and proteins. Proteins, for the most part, do all of the grunt work in the cell: giving it structure and shape, as well as performing the cornucopia of chemical reactions that keep life living (yes nucleic acids can be catalytic or structural [see: ribosomes], there’s exceptions to every rule that are SUPER cool, unfortunately I cant learn EVERYTHING about everything).
DNA is a cell’s instruction manual. It contains the necessary information to make every single possible protein in the repertoire of a particular organism. Ribosomes are the cell’s construction crews: they make all of the proteins. Ribosomes cant read the directions in the DNA directly. Ribosomes are only able to read RNA, which is basically DNA’s single-stranded, chemically unstable cousin.
When a ribosome uses the instructions encoded in RNA to make a protein, it’s called translation. For translation to happen, another machine in the cell, called RNA polymerase, uses the DNA as a template to make a piece of RNA. Every cell doesn’t need to make every single possible protein all of the time. So, when a cell needs to make a protein, RNA polymerase finds the gene that codes for the protein in the DNA, transcribes the gene to make a piece of RNA, then a ribosome translates the RNA to produce a protein. To torture a metaphor: Ikea makes a lot of different kinds pre-fab furniture, and has the directions to assemble every single piece of particleboard. The directions happen to be in Swedish. When you want a coffee table you need to get a copy of the English directions, which you follow to make a Vittsjo. You DON’T need the instructions to make a Grundtal in your living room, so you don’t need the English version of those instructions.
My favorite machine in the cell is called the replisome. The replisome’s job is to copy the DNA. The replisome is really good at its job, but sometimes it needs to copy a region of the genome when RNA polymerase happens to be making RNA from those genes: conflicts occur between replication and transcription.
I study what happens to the DNA when the two machineries bump into each other. It turns out that quite a lot can happen: the replisome gets stuck, the DNA can break, and mutations can occur within the genes. I’m interested in how these processes affect the bacteria. I’m especially interested in how the mutations that do occur as a result of conflicts between replication and transcription impact evolution in bacteria.
This conference will have a session all about replication-transcription conflicts. They happen in all organisms, and have been linked to mutagenesis leading to autism, fragile-X syndrome, and even cancer! I’m super stoked to hear about what other people in my field are researching, but the conflicts session is just one out of eight!
DNA is an amazing molecule, and it does some pretty crazy things in our cells. We think of DNA as being a double helix. However, whenever DNA does something interesting for biology like getting copied or transcribed, it needs to be opened up into the two individual strands. When DNA is single stranded, it can start to do some pretty amazing acrobatics. DNA will form hairpins, cruciform structures, triple helixes, and non-canonical base pairs.
Sometimes, if the sequence is right DNA will knot itself up into a structure called a G-quadruplex that is so stable it stands up to being boiled in acid for 15 minutes. G-quadruplexes happen in our cells, and they can seriously mess with how a gene gets turned on and off.
Sometimes DNA will base-pair with its unstable cousin RNA to make a structure called an R-Loop. R-loops are a serious roadblock for my favorite machine, the replisome.
When DNA gets broken, it is repaired by a process called homologous recombination. For recombination to happen the DNA gets into a complicated conformation called a Holliday junction. It’s vitally important for cells to sort out these structures correctly, otherwise they run the risk of breaking the DNA further or losing genetic information.
I’m going to be learning about a panopoly of parlor tricks that my preferred nucleic acid performs. I could not be more excited for the week ahead.
I’m about to have science coming out of my ears, so I’m going to be taking a brief hiatus from blogging until I return to Seattle. Rest assured that I’ll be waking up early every morning to run around Itasca and think about chromosomes, but I’ll be posting fewer selfies in the coming days. I hope everyone has a blessed, wonderful week! I’ll catch everyone on the flip-side.