CONTENTS Cell Motility pg 2
Saltman Quarterly
Marine Microbes pg 3
Menstruation & Exercise pg 4
Volume 23 | Fall 2023
MOTION COVER PHOTO BY INAYA NICHOLLS
SQ INSIDER
CELL MOTILITY:
SWIMMING
A FIGHTING CHANCE WRITTEN BY: JIHYUN IN | ILLUSTRATED BY: LINDSEY KIM INTRODUCTION
It would by no means be a stretch to say that our survival is dependent on our ability to move. We move to find food, breathe, blink, speak—the idea of “doing” anything means we must move. As it turns out, it’s not much different on the microscopic level. Whether it be to avoid toxic environments or chase after nutrients, cells depend on motion to survive too. One particular system that relies on motion to keep us alive is the immune system. The immune system employs an incredibly complex and powerful team to keep your body safe. Pathogens are everywhere and can enter the body at any point, constantly putting the immune system to work. We maintain an army of cells within our immune system in order to find these pathogens. What good would that army of immune cells be if it weren’t able to chase down the pathogens? On the other side of this microscopic war, different enemies are looking to take over your body as well. After all, if they didn’t have any tricks up their sleeve, no one would ever be sick! Many of these “enemy” cells also employ different methods to move effectively. So far, we’ve established that there can be an active war within the body, where the immune system works to fight intruders. Much like a game of tag, where both parties are running, both the immune system and the intruders have methods of chasing and being chased. Let’s take a look into some of these different methods.
CRAWLING
On our side, the T-cell, a type of white blood cell in our immune system, targets and attacks only the infected enemy cells. To do so, T-cells employ the art of “crawling” to catch their pathogenic prey. This involves two parts: sticking to a surface (mostly blood vessels) and crawling to move forward. To crawl along a surface, the cell must first attach itself to the surface and exert a force on it. Even within a single cell, adhesion strength differs: it is generally stronger towards the “front” of the cell and weaker towards the “back”. Here, the front of the cell refers to the forward, leading-edge of the cell that faces the direction that the cell is trying to move in. The polarity of cell adhesion allows the cell to detach its back end from the surface, promoting forward movement. The actual movement occurs through rapid polymerization and depolymerization of a polymer known as actin, which forms a majority of the cytoskeleton. During cell movement, actin molecules rapidly assemble near the front of the cell (polymerization), while the actin molecules in the back end disassemble (depolymerization). This growth often organizes into thin, sheet-like 2D protrusions at the forward edge of the cell, known as lamellipodia. In T-cells, an enzyme called RhoA regulates this process; depleting the cell of RhoA leads to a lack of lamellipodia. Comparison of RhoA knockdown cells—cells that have been modified to have reduced RhoA gene expression—and control cells revealed that the knockdown cells formed multiple narrow projections rather than a single lamellipodia. In addition, the knockdown cells moved at significantly slower speeds.
Editors-in-Chief: Amoolya Chandrabhatta, Emily White Executive Editor: Sharanya Sriram Editor-at-Large: Chiraag Kambalimath Head Production Editor: Jacqueline Cheung Head Illustrator: Kristiana Wong
On the enemy’s side of the battle, one way that many bacteria like E.coli and H.pylori move is through their tails, known as flagella. The flagellar motor, a rotary machine at the base of each flagellum, spins the flagella and causes the cell to propel forward. The lengths of the flagella are vital in this process; if the tails are too short or long, they are less effective. Like Goldilocks, the cells keep the lengths just right. Cells display incredible control over this length, as they are able to grow flagella back to their original length after amputation. Though the mechanism of how a cell does this is not clearly agreed upon, one proposed model is the Time-of-Flight model, which hypothesizes that the cell can measure the amount of time it takes for supplies to reach the tip of the flagellum and return. In this model, the cell is hypothesized to attach a “timer” molecule that switches states randomly at a certain rate. Depending on the state the molecule returns in, the cell then decides whether it should send more building supplies or not. Other mechanisms of length sensing have been proposed as well, such as the ion-current and diffusion models. By sensing the length of their flagella, cells with multiple flagella are also able to keep their lengths approximately even. Of course, nothing is perfect, and mutations can negatively affect flagella. A substitution mutation in the gene that produces the FliM protein, a protein that forms the rotor of the flagella, results in an increase in the number of flagella in Vibrio alginolyticus, a marine bacterium responsible for many wound infections, leading to reduced cell motility. Flagellar length can be altered through mutations as well, and even small alterations lead to significantly decreased cell motility.
PSEUDOPODIA
Taking a page out of the crawling-book, cancer cells can also migrate using actin polymerization, but with a twist. Unlike the thin lamellipodia, these protrusions can be 3D structures and are instead called pseudopodia. In addition to cell motion, the pseudopodia work to penetrate and move through the endothelium—the cells that line the various organs and cavities throughout the body. The 3D structure helps the cell to be more efficient in probing and getting to nearby spaces. This helps the cell relocate to different parties, which drives metastasis, or the spreading of cancer. The neutrophils of our immune system also like to use pseudopodia. Neutrophils are non-specific white blood cells, meaning they can attack any microorganism they come into contact with. In neutrophils, pseudopodia facilitate direction change by dynamically changing their protrusion direction, thereby helping the cells move in that direction. The broad shapes of neutrophil pseudopodia also help the neutrophil to search more space quickly. This makes for an efficient system of movement. Like any war, it is important that our immune system and its enemies are properly equipped with methods of motility to chase and be chased. In this article, we’ve explored some of the ways our cells can move: cells can crawl through cell adhesion and polymerization, swim using their flagella, or even probe and penetrate with pseudopodia. There are also other ways cells can move, such as blebby migration. Next time you’re sick, you can get plenty of rest knowing the hard battles taking place within your body!
Staff Illustrators: Lindsey Kim, Jenny To Head Photographer: Harnoor Sidhu Staff Photographers: Inaya Nicholls, Darren Wong Head Tech Editor: Nicolas Bello
Fall 2023 | Vol. 23| 2
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WRITTEN BY: MICHAEL MCCLELLAN ILLUSTRATED BY: JENNY TO
R IN E M A IC M
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L MOTIL A I B IT O R
Y
arm sand juxtaposes the cool ocean breeze, while the briny smell of dimethyl sulfide fills the air. You look up to a cloudless sky as a few pelicans pass on by. Perhaps you’ve been here many times before, or maybe it’s your first time. As you roll your pants up and begin to wade into the deep, blue expanse, you may not be thinking about the millions of marine bacteria surrounding you and their significance in maintaining the world’s largest ecosystem. You’re also probably not thinking about marine motility, one of the most important characteristics that only a small percentage of marine bacteria possess. The word “motility”, related to “chemotaxis”, the movement of motile cells in response to chemicals, is often confused with the word “mobility”. While “mobility” is a more general term that relates to the ability to move or be moved, “motility” refers to a cell’s ability to self-propel through the utilization of metabolic energy. Although motility can be achieved through different means, many bacteria use flagella, a very thin appendage, to self-propel. However, as we’ll see in a strain of cyanobacteria reviewed later, not all bacteria need flagella to be motile. There are five different types of motility: swimming, swarming, twitching, gliding, and sliding. Although swimming and swarming motility both utilize flagella to create cellular movement, swarming refers to the movement of multiple cells, while swimming refers to the movement of a single cell. Twitching, gliding, and sliding motilities use different methods to produce movement over particular surfaces. For example, in twitching motility, the type IV pili, an appendage important for bacterial adhesion and colonization, extends and retracts to create bacterial movement. Furthermore, bacteria that demonstrate sliding motility use surfactants, substances that reduce surface tension, to selfpropel. These types of motility are not mutually exclusive, meaning that under certain circumstances, the same bacterium could utilize a different type of motility. For example, the freshwater marine bacterium Pseudomonas aeruginosa exhibits swarming motility when exposed to particular nitrogen and carbon sources but exhibits sliding motility when no hairlike appendages like pili or flagella are available for self-propulsion under the same nutrient conditions. Motility proves to be an extremely important characteristic for marine bacteria, especially for those situated in oligotrophic environments, or environments that lack an abundance of nutrients. By moving from unfavorable conditions to favorable ones, bacteria avoid toxic substances in their respective environments. Motility allows bacteria to move to areas with higher levels of nutrients, positively benefitting their own nutrient uptake and affecting nutrient cycling in marine microecosystems. Additionally, motility allows for unique host-associated processes like colonization, where a cell or microorganism can grow and multiply in or on a host without harming or disturbing the host itself. Through chemotaxis, motility allows bacteria to move and access hosts, further contributing to their ability to colonize these hosts. Motility allows bacteria to evade harmful predators like bacteriophages, which are invasive viruses that kill bacteria. While motility presents multiple benefits to bacteria, it also has its drawbacks. For example, it takes a large amount of metabolic energy for a bacterium to self-propel. As a result, bacteria cannot constantly move for extended periods of time. Synthesizing appendages such as flagella and pili, as well as their individual components, is also energetically expensive. Additionally, in parts of the ocean that experience little change in unique bacteria, horizontal gene transfer, or the transfer of genetic material between organisms that do not have a parent-offspring relationship, may not be readily available, further suggesting that motility is unachievable. In order for a bacterium to be motile, it must possess a particular set of genes required for motility, but if those genes are not available in other organisms or bacteria in its environment, then the bacterium will not be able to obtain them.
Despite these drawbacks, research by Hibbing et. al shows the benefits of microbial motility through a comparison of non-motile and motile bacteria. In his work, he shows that motile bacteria often outcompete their nonmotile counterparts, as motile bacteria move to areas where nutrients are more readily available, or avoid microbial competition entirely through their motility. Additionally, Hibbing’s research shows that motile Pseudomonas aeruginosa, when competing with its non-motile variants, moves to the surface where rich nutrients are more easily accessible, while the non-motile bacteria cannot. Studies show that only a small fraction of marine bacteria demonstrate motility, often requiring appendages to facilitate cellular movement processes. However, research conducted in 2003 by Dr. Palenik et. al at the Scripps Institute of Oceanography uncovered a specific strain of the marine cyanobacterium Synechochoccus, WH8102, that lacks the full set of genes necessary for appendage functionality, yet still demonstrates a unique form of swimming motility. The strain developed motility traits most likely as a result of horizontal gene transfer through phages, as WH8102 Open Reading Frames (ORFs), specific spans of DNA sequences, demonstrate genomic differences in comparison to those of a closely related, reference marine cyanobacterium, Prochlorococcus. More recent research at Scripps Institution of Oceanography revealed extreme ocean conditions’ effects on marine motility. In May 2023, Mullane et. al observed marine microbial motility at low temperatures and high-pressure conditions in the ocean, discovering that low temperatures had largely negative implications on motility, more so than the effects of high pressure (10 to 50 Megapascals). This was because low temperatures decreased flagellar rotational speed, hampering bacterial self-propulsion. Additionally, flagellar synthesis was negatively impacted by low temperatures, causing ineffective motility. Depending on the stresses of low temperature and high pressure, motility either regressed then returned, or was completely lost as a result of flagellum non-functionality. Although great progress has been made in understanding marine microbial motility and bacterial motility more generally, questions surrounding microbial motility’s effects on nutrient cycling and bacterial survival in marine ecosystems persist. Maybe you’ll be the next person to answer them.
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hen we start consistently exercising, we expect gradual physical improvement in response to our effort. Many of us implement a daily activity goal or a weekly workout schedule in hopes of achieving our desired results. After all, we often structure our lives day to day: get 8 hours of sleep, go to work or school, and take care of ourselves physically and mentally; all over 24 hours. But what if the 24-hour cycle isn’t the best way to meet our fitness goals? This may be the case for those who menstruate, as their bodies operate on a different, much longer cycle. The menstrual cycle can be characterized by either the ovarian cycle (changes in the ovarian follicles) or the uterine cycle (development of the uterus lining). Each phase is accompanied by changes in hormones known as estrogen, which grows the uterine lining and ovarian follicles, and progesterone, which maintains the uterine lining for proper egg growth. The ovarian cycle in particular is divided into three phases: the follicular phase, ovulation, and the luteal phase. The follicular phase starts when the ovarian follicles (small sacs in the ovary that contain estrogen, progesterone, and the maturing egg) begin growing; it can last anywhere from ten to twenty-one days. The follicular phase also starts with the period and is accompanied by increasing estrogen levels. Immediately thereafter, luteinizing hormone (LH), which regulates hormonal levels and cycle length, also peaks, leading to ovulation. During ovulation, the follicles mature fully and release an egg. In the luteal phase, estrogen levels decrease while progesterone levels increase to prepare the uterus for pregnancy. If pregnancy does not occur, progesterone levels also fall, signaling to the brain to restart the cycle. Currently, most research on the menstrual cycle explores hormone levels and their effect on muscular strength and musculoskeletal recovery. A study done by Phillips et al. at University College London in 1996 tested the effects of menstruation on muscle strength in four groups: female athletes, sedentary menstruators, those using oral contraceptives (OCUs), and men (as a
control group). Muscle strength measurements consisted of the muscle force (an average taken from three to five trials) generated by contraction of the adductor pollicis muscle, located in the hand. To quantify their results, they recorded the difference between the muscle strength generated during the trial and the average taken previously. They found that muscle strength had a greater peak difference from the average during the follicular phase and ovulation, compared to the luteal phase in the athlete group and the untrained menstruators, whereas there was no significant difference observed in men and OCUs. Furthermore, a University of Oklahoma study by Kersick et al. in 2008 demonstrated significant differences between the levels of exercise-induced muscle damage and oxidative stress— the buildup of harmful oxygen products—in women (specifically during the mid-luteal phase) and men. Women had significantly less risk for both factors, which led Kersick to hypothesize that musculoskeletal recovery could be linked to hormone levels. Women were also found to suffer from greater levels of muscular damage and oxidative stress during the follicular phase than the luteal phase. Knowing that hormone levels may impact muscle recovery, how might we incorporate these findings into our exercise routines? One possible program is “phase-based training,” designed to follow the follicular and luteal phases of the menstrual cycle. During one phase (either follicular or luteal), high intensity workouts are prioritized, while low intensity workouts are utilized during the other phase. High intensity workouts include weight training and HIIT workouts, while low intensity workouts typically constitute light weight training, steady-state (LISS) cardio exercise like walking, and yoga. A 2022 study by Kissow and colleagues at the University of Copenhagen found that follicular-phase based training yields more muscle growth and better performance than lutealbased training or phase-independent training. By synthesizing results from previous studies, Kissow found that quad muscles had more muscular strength after utilizing high intensity workouts during the follicular phase instead of the luteal phase. But why might these changes exist in those who menstruate in the first place? Estrogen’s role as a steroid hormone may provide some explanation. Generally, steroid hormones regulate gene transcription, leading to protein production in cells, which helps muscle growth and repair. More specifically, estrogen participates in protein kinase signaling pathways in skeletal muscles, which activates certain promoters and transcription factors, facilitating gene expression, including genes that code for muscle and tissue growth. Estrogen also activates satellite cells, stem cells that precede skeletal muscle cells and aid in the musculoskeletal regeneration process. Furthermore, estrogen inhibits protein catabolism, a process used to provide more energy for the body. Because estrogen levels are typically greater in the follicular phase and ovulation, inhibition of protein catabolism may explain why there is more exercise-induced muscle damage associated with the follicular phase than the luteal phase. However, not all research on the menstrual cycle has yielded the same results; some studies show minimal effects of menstrual hormones on biological processes involved in exercise performance and recovery, especially relating to carbohydrate metabolism. In a study performed by Horton et al. in 2002 at the University of Colorado Denver, researchers found the menstrual cycle had no effect on glucose metabolism, which involves processes like glycolysis and cellular respiration. These processes break down glucose into energy, aiding exercise performance by promoting muscular contraction. Furthermore, another study by Campbell and colleagues at the University of Melbourne found no difference in glycogen use across menstrual phases. Glycogen breaks down into glucose, which further metabolizes to provide energy for the body and fuel exercise. While further research is required regarding exercise training in accordance with the menstrual cycle, we can still implement some of these findings into our lives. For those that utilize resistance training, try structuring your workouts to involve more high-intensity work during the follicular phase and more recovery-focused low-intensity work during the luteal phase, and observe the results. After all, no cycle is the same; some menstruators may follow a 22-day cycle, while others may need to synchronize their workouts over a 30-day period. What’s most important is finding what kinds of physical activity works best for you, and when.
THE MENSTRUAL CYCLE & EXERCISE PERFORMANCE
WRITTEN BY: ISHA TRIPURANENI PHOTOGRAPHED BY: DARREN WONG
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