Inspired by this XKCD Up-Goer Five comic (and aided by this Up-Goer Five text-editor), we present three cases of complicated science made… simpler. Graduate students Tom Aunins, Kaitlin McCreery and Max Levy describe their research only using the 1,000 most common English words.
Most of the time, the good creatures in our bodies throw nice parties and get along just fine. But sometimes, tiny bad creatures join the party and try to start fights. When this happens, we use special drinks to kick out almost all of the creatures, good and bad. A small number of the bad creatures are too strong and cannot be kicked out, so they do not leave when we take the drink. Once the drink has run out, and most of the creatures are gone, these strong bad creatures have lots of room to take over the place. When this happens, we have no way to push them out! Instead of a drink that tries to push everything out and misses some creatures, we need a drink that kicks out only bad creatures but keeps the party going for everyone else.
We learned that the bad creatures often say bad words that only the bad creatures know. We created a new kind of drink that looks for creatures that are saying these bad words, and it kicks them out of our party/bodies. Once we know which words only the bad creatures say, we can make drinks that kick out all the creatures that say those words, and leave the good creatures alone.
Many of the most commonly used antibiotics today are broad-spectrum antibiotics, targeting a wide array of bacteria (i.e. both gram-positive and gram-negative.) These antibiotics work by inhibiting processes that are common to many different species, like cell wall synthesis or protein translation. Unfortunately, this means that these antibiotics can also wipe out beneficial microbes. Sometimes, these broad-spectrum antibiotics leave behind a subset of antibiotic-resistant bacteria that grow unchecked. The spreading of antibiotic-resistant bacteria, and the passing of antibiotic resistance genes from cell to cell, has alarmingly increased the rates of resistance to even our most potent drugs over the past couple of decades.
I am developing a species-specific alternative to broad-spectrum antibiotics that utilizes peptide nucleic acids, or PNAs. PNAs are DNA-like single-stranded molecules that combine nucleotide bases with a stable peptide backbone. These PNA molecules bind to the mRNA of essential bacterial genes, preventing the bacteria from translating the proteins they need to survive. The goal of my research is to find essential genes with unique starting sequences in pathogenic bacteria like E. coli or K. pneumoniae so that we can design a therapy that targets only that species, leaving others unaffected. Effectively, I aim to address one key cause of antibiotic resistance.
Our body is made of tiny building blocks of life. The ground that you build these blocks on controls what shape they will take. I study “simple” blocks of life that can grow up to become any other kind of life block, like the “special” blocks used for building body parts like hearts and brains. When you are tiny, you start out as a lot of simple blocks. These simple blocks change into special blocks that help you become a human with different parts like arms, legs, a stomach, and a brain. These simple blocks change into special blocks by talking to the blocks next to them, or by touching something hard or soft. To explain further, a simple block that touches something will become a hard block (like a heart block), and one touching something soft will become a soft block (like the kind that make up your brain). I try to confuse the simple blocks by changing the ground below them—from hard, to soft, to hard again. Then I look at how the blocks act; maybe they remember what they were touching last, and stay as simple blocks, or maybe they will keep changing between hard and soft building blocks. I especially want to see how the building blocks that make up your brain and heart would act on a ground that changes how hard it is. This could help me understand how brain blocks can get sick, and how to grow better hearts for people when their hearts stop working.
Cells are dynamic structures that change their function in response to changing stimuli in their environments. These stimuli can cause a change in cell surface stiffness, cause the cells to anchor to a surface, or even change cellular shape. This adaptability is particularly important for stem cell differentiation, although all cell types retain a mechanical memory of the stiffness of past surfaces they have been cultured on.
By changing the mechanical stiffness of the culturing surface, we observe changes in cell migration and stem cell differentiation. Over the last decade, using surfaces with etched micropatterns has become a very popular way to study cell-surface and cell-cell interactions. I am building a micropatterned culturing substrate that can reversibly change its elastic modulus, or surface stiffness. I am constructing these surfaces to have micro-sized cantilever beams, and use magnets or fluids to change the stiffness of the beams. Designing dynamic substrates may be able to trick a cell’s mechanical memory, which can benefit tissue engineering.
When we feel sick, it is often because bad little creatures are visiting our bodies. Doctors help us feel better by giving us “bad little creature killers”. These creature killers usually work quite well. But now more than ever, doctors are seeing sick people that we cannot help by using the creature killers. This is because these aren’t just the usual bad little creatures that make people sick…these are some really bad little creatures. Because there is no good way to completely kill these really bad little creatures, many people remain sick for a long time. Some even die!
To help these very sick people, we are working to understand how to kill the really bad little creatures. We use tiny little power rocks that attack the really bad little creatures with shots of “killing power”. The rocks are so tiny that they can go inside the creatures without the creatures noticing. The tiny rocks get their power because we hit them with light, making them really excited. The rocks can’t stay excited for very long, however, so they turn their excited feeling into shots of killing power. The killing shots fly away from the tiny rocks in every direction, hurting the creatures from within. By controlling how much light and how many rocks we use, we can control the killing power. That way, the tiny rocks kill only the really bad little creatures that make us sick without bothering the bigger creatures that help us live. The rise of really bad little creatures is a big problem for the world, and we hope our tiny little rocks help stop them.
Most bacterial infections can be treated by normal courses of antibiotics. However, cases of drug-resistant bacterial infections are growing rapidly. Such afflictions often have no robust treatment, causing thousands of deaths annually. To develop novel treatments, researchers have focused on understanding how reactive oxygen species (ROS), highly unstable molecules that damage cellular components and impair cell function, can cure these drug-resistant infections. In our lab, we use light and nanoparticles to generate superoxide, a form of ROS that causes damage on critical intracellular components. Controlled doses of superoxide can kill multi-drug resistant bacteria while leaving mammalian cells unharmed.
To generate superoxide, we engineer quantum dots, semiconductor nanocrystals, to have specific electronic properties. We activate our quantum dots by using visible light. Upon absorbing this light energy, electrons in the quantum dot become excited and transfer to oxygen molecules available in the surrounding water. This process creates superoxide radical that freely diffuse around the cell, damaging proteins, DNA, and lipids which kills the cell. The rise of drug resistant bacteria is a global health concern, and we hope that our research will lead to a viable treatment solution for those afflicted.