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Author: Emily King
Teamwork in the workplace is vital. Co-workers need to support each other under pressure. When this breaks down, everything can fall apart.
In this regard, your daily office antics are a clue to how mitochondria might cause diabetes. Aside from being the powerhouse of the cell, mitochondria juggle multiple responsibilities. Their role in skeletal muscle is highly stressful. Under stressful conditions, the connected network of mitochondria or “reticulum” is crucial. Mitochondria consistently look out for each other through mitochondrial fusion and fission. Fusion allows mitochondria to share healthy parts, like colleagues swapping tips. Whereas, fission isolates damaged parts, prior to repair or disposal. Fission is like taking poor-performing staff aside for a final warning. Their work will improve, or they’ll face termination of employment. When mitochondrial fusion and fission are balanced, the environment is highly productive. Muscle can do its job. Metabolism, a key responsibility of muscle, relies on mitochondria and sugar. After we devour our sweet treats, sugar causes the pancreas to release a hormone called insulin. Insulin then moves sugar from circulating blood into inside our cells. There, it is greeted by mitochondria and converted to fuel for bodily processes. Muscle takes up almost half of our weight and is packed full of mitochondria. It uses a lot of sugar, 80% of what’s available, to be precise. However, this ability of muscle is reduced in people experiencing Type 2 Diabetes. That’s one in 11 adults worldwide! Mitochondrial cooperation, or fusion, appears to have dropped. This shifts the balance more towards mitochondrial fission. The disturbed equilibrium means inefficient mitochondria, which can cause blood sugar to rise. This impact on the body is known as pre-diabetes. The body compensates by producing more insulin to drag sugar from the blood to cells. Unfortunately, this is unsustainable. It can eventually lead to insulin resistance, a key risk factor for Type 2 Diabetes. Sugar escapes to places it shouldn’t. It wears down organs, like energy levels over a long work week. Long-term blood sugar levels above the accepted range can lead to complications of diabetes. If you want healthy eyes and kidneys, plus full use of your limbs, this is not for you. But how do we avoid it? I’m asking you to reconsider your view. People with Type 2 Diabetes may not be couch potatoes or gorge to their heart’s content. Race, age, gender, genetics, and mitochondrial dysfunction can all play a part in the disease. Mitochondria don’t get to book a long weekend for rest and relaxation. They work tirelessly, at increased risk of burnout. When overworked and stressed, mitochondrial productivity can plummet, just like ours. This triggers a series of damaging events in the body that are linked to Type 2 Diabetes, cancer, and Alzheimer’s Disease. Despite all of this, mitochondria are currently not the main focus of Type 2 Diabetes treatment. The major players are healthy nutrition and exercise. This is followed by medication for further blood sugar control. In theory, exercise studies have proven benefits for mitochondrial health. But we are real-world people, not robots! We know we *should* stick to an exercise regime, but it’s a major hurdle, even when healthy. On the diabetes drug front, metformin, the first-line choice, interacts with mitochondria, though the exact nature of this interaction is hazy. My PhD research aims to develop a new understanding of how mitochondria might cause Type 2 Diabetes. If we gain knowledge of the faulty mechanism, we can fix it. We can take steps like re-establishing fair division of labour between muscle mitochondria. By taking a new approach to treat Type 2 diabetes, we can add an extra bow to our treatment arrow aimed at this complex disease.
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Author: Kerry Silva McPherson
Barring some glaring exceptions, I’m rather impressed with the US’s reaction to the COVID-19 pandemic. After witnessing climate change denial, flat earth theory, and the anti-vax movement, I didn’t have faith that the American public would be proactive about a viral pandemic.
I was certainly proven wrong (again, with blatant exceptions). To slow disease spread, the CDC advised the public to take preventative measures, and Americans listened. Well before state and federal governments mandated school and business closings, the private sector acted. Professional sports, Broadway, and movie theaters canceled games and shows, voluntarily forfeiting profits for the sake of public safety. Colleges and universities prudently moved classrooms online before governors announced mandatory cancellations. Clearly, we are capable of putting aside comfort, money, and ambition for the security of public health, so why are we not willing to do the same when it comes to climate change? Our health and safety are not only at risk due to Covid-19, climate change is an ever-present threat to human health, and it’s time for action. Flattening the global temperature curve. 
With a 1°C increase of the earth’s temperature, 2019 was the second hottest year on record. 1.0°C may seem trivial, but the United Nations predicts another half-degree of warming could be catastrophic in terms of coastal flooding, droughts, and heatwaves. When Covid-19 cases were low in number, the importance of social distancing, telecommuting, and hand washing was understood. Similar to Covid-19, the sooner we act to mitigate climate change, the more damage we avoid. And like the pandemic, we do not have to wait for the government to layout regulations.
Learning from mistakes The reaction to the pandemic was far from perfect; we should learn from our errors. Firstly, we need leaders who can deliver calm, accurate, and useful information. Political affiliations aside, President Trump did not have the rhetoric or composure to address a global pandemic. 2020 is an election year for the president, 33 senator seats, and 11 State governors (US). This is an opportunity to elect leaders that listen to scientists and speak honestly with the public. Secondly, we need to prepare for health-related crises. The shortage of masks and gloves for health care providers is inexcusable, and the lack of a financial plan for a pandemic is shameful. Climate change causes oceans to rise, insect-carrying diseases to flourish, and wildfires to spread. The government needs to have the resources and money to respond to these events, which scientists warn are inevitable as climate change perpetuates. If we are fortunate, the Covid-19 pandemic will peter out, and our social and work lives will continue. From this experience, we should remember that our health and safety are not guaranteed and that we need to work together to ensure our well-being.
Author: Ethan Kim
Work-life balance is really hard to achieve – it's like a myth. Something you hear about, like Bigfoot or the Loch Ness monster – but never seem to actually see in real life. In undergrad, I struggled with burnout often. So, when I entered grad school and into an unfamiliar field of study, I wanted to go in with a plan: balance my life between work, my side-hustle, and my personal life. If there's anything my undergrad taught me, you have to do your research before you plan out an experiment. So, I did some research on what burnout is and why exactly it's corrosive to our physical and mental health. I also started to experiment with some self-care, and I'll share three tips that I've personally found really helpful! What is burnout? Not a lot of people knew what burnout exactly was when I asked them. To be fair, I only vaguely knew what it was until I felt it in undergrad. But once I started researching burnout to write this post, I went down a deep, deep rabbit hole (as you do when you search up a topic at 3 AM in the wee nights of dawn) and found some rather not-so-great statistics from a few key studies. So, what exactly is burnout? The World Health Organization (WHO) defines it as an "occupational phenomenon" in their International Classification of Diseases, meaning that it isn't a medical condition – yet. I have a strong suspicion that soon enough, it will be considered a medical diagnosis, similar to how the WHO declared stress as the health epidemic of the 21st century. The WHO defines burnout as: "a syndrome conceptualized as resulting from chronic workplace stress that has not been successfully managed." They characterize it in three ways:
Interestingly, burnout is specifically defined as "chronic workplace stress" - but I've felt it from just studying and taking exams. Maybe that gives more credence to the idea that studying and doing exams are work? Impact of burnout on the economy and health I'll highlight two studies that I thought were the most disturbing for our health and the economy. The first is a study conducted at Harvard in 2015, concluding that workplace stress contributes to at least 120 thousand deaths a year in the States. To put that into perspective, workplace stress would've been at number 6 in the top 10 list of the causes of death in the States in 2015. The other 5? Heart disease, cancer, chronic respiratory disease, accidents, and stroke. Mind you, they defined ten workplace stressors, and some of these aren't things you would experience directly at work, like unemployment. But, stressors such as high job demands and long working hours experienced by many fresh grads in their first job, whether that's as a graduate student or outside of academia. "That's wild," I thought, and I went further down the rabbit hole. The WHO published an information sheet about workplace stress in May of 2019, and one point was staggering to read. Depression and anxiety cost the world an estimated $1 TRILLION (US) dollars in 2019. There were some work-related risk factors identified in this information sheet, some of which included:
It's unbelievable to me that despite the negative consequences of overworking and the resulting stress, grad students and employees are often working way more than 8 hours a day. In my undergrad, I felt that it might be the culture – "if you're sleeping, you're falling behind" was a running joke in our friend group, but at times, it felt true. I could be doing another problem set, or reviewing my notes, or reading another paper. Sleeping felt guilty at times – but I learned much later that sleeping was helping me learn, which is a bit counterintuitive. So, here's a couple of things I've started that help me achieve a bit of that mythical work-life balance. Hopefully, you'll find them useful! Meticulously plan out your week. I was determined to have my weekends (relatively) free. So, to make the most out of my weekdays, I started to plan out my day almost by the hour. I found that by being intentional with my time, I stuck to my plan better and was doing more than I thought I could ever do in a week. While it hasn't been perfect, I've definitely had freer weekends to destress and sleep-in. On the other hand, my time at my lab has been packed (although, as of writing this, COVID-19 is on the horizon and, I may end up working from home). While it's been busy, taking breaks every 30 minutes to rest my eyes and let my brain relax for a bit has been super helpful! Sleep. Like, properly sleep. Sleep is amazing, and so are the benefits that you get from sleeping the recommended 7-8 hours.Better working memory, helping you retain and synthesize things you learned throughout the day, and cleaning the brain of harmful waste products are all benefits of sleep. There are tons of studies linking the lack of sleep to host of health problems. While the occasional all-nighter isn't the worst thing in the world, chronic sleep loss leads to irritated moods, mental health issues, memory problems, and cardiovascular problems. But sleep a regular 7-8 hours a day, and you'll get benefits like better working memory, more energy throughout the day, and better brain health. What I mean by that is your brain gets to clean itself - yeah, you heard me. Clean itself. Your brain alone uses almost 20% of your energy per day, so it produces a lot of waste as a by-product of energy use. These harmful by-products are related to diseases like Alzheimer's and other brain-related diseases. So, by sleeping, you allow your body to get rid of those waste products and, in turn, help you be ready and healthy. Take up a hobby! Research shows thatthose who have a hobby can be more creative and productive outside of work. While it's weird to say, I've taken up coding as a somewhat necessary hobby. I know it's a bit hypocritical, but instead of coding for my research project, I'm learning how to code to expand my skill set and create side-projects that might be interesting. Also, gaming with friends really seems to help me enjoy my time off from work. I'd get asked if I had a life outside of work before, and I couldn't answer "yes" as I'd go home from class, study, eat, study… and rinse and repeat. Now, I can confidently say "yes" and be happy that I do stuff outside from reading papers and doing research! So to cap it all off, here's the TL;DR (too lazy, didn't read): Burnout is characterized by feelings of exhaustion, negativity and cynicism towards your job, and reduced efficacy at work. It's caused by poorly managed workplace stress, which can have catastrophic effects on our economy and health, being deadly enough to place it in the top 10 causes of death in the states. Things you can do (for free!) to help you combat burnout and be more productive at work are planning out your days, sleeping the recommended 7-8 hours, and taking up a hobby. I learned a great deal about burnout and productivity – maybe give a search on Google and see what you can learn outside of what my summary details!
Author: Yuezhe Li
Ever since green fluorescence protein was discovered in jellyfish, fluorescent proteins have been widely used in biological studies to tag their protein-of-interest with different colors of fluorescent proteins. What is less often talked about is that fluorescent protein tags can completely mess up your experiments by changing the behavior of your protein-of-interest.
Many fluorescent proteins are engineered with a special goal in mind; pHluorin is an example. It was engineered to mark out secretion events in cells. pH changes when secretion occurs. Inside secretory granules, the environment is acidic. In the extracellular space, the environment is neutral. pHluorin emits low fluorescence in an acidic environment and is brighter in a neutral environment. This means that when a protein with a pHluorin tag is secreted, a puff is observed (see video).
When your secretion marker prevents secretion The postdoc in my lab is interested in studying protein secretion. He uses a mouse pancreatic β cell line that secretes insulin to study this process. To capture secretion events under the microscopy, he used pHluorin-tagged insulin that is supposed to give puffs when secretion happens, as discussed before. Yet somehow, despite literature suggesting YFP-tagged insulin is secreted in β cell lines in response to glucose stimulation, the postdoc did not observe similar phenotypes when he used pHluorin-tagged insulin. In theory, pHluorin is a much better secretion marker than YFP, because it is more sensitive to pH. However, he saw little puffs after cells were stimulated. Out of desperation, my PI asked him to test whether GFP-tagged insulin is secreted. The fluorescence intensity change of GFP in response to pH change is similar to pHluorin: lower in acidic pH, brighter in neutral pH, but is less sensitive than pHluorin. To everyone’s surprise, he observed ample secretion events when he used GFP-tagged insulin! It is never clear why pHluorin-tagged insulin cannot be secreted efficiently. After all, pHluorin has been used in secretion related studies for years. However, it is always a cautionary lesson that your seem-to-be-perfect fluorescent protein tag can be the one causing trouble. When your new brighter fluorescent protein tag changes receptor localization I am interested in studying insulin receptor localization and signaling. It was previously observed that insulin receptors localize to a specific organelle, the primary cilium, under some conditions. I was interested in how this localization changes insulin receptor signaling and the kinetics. I observed this localization using immunofluorescence and probed for the GFP-tagged insulin receptor. However, I could never capture the receptor within the proper localization when I used the mNeonGreen-tagged insulin receptor. My Western blot gave me a tantalizing clue. To my surprise, the Western blot showed the two differently-tagged receptors have very different molecular weights. This should not be the case, because these two fluorescent proteins were similar in weight, and the insulin receptors were tagged the same way. Further immunostaining showed that while GFP-tagged insulin receptors localized to the plasma membrane, the place the insulin receptor should have been, mNeonGreen-tagged insulin receptor did not localize to the plasma membrane, instead, it was inside the cytoplasm! To conclude, we think the different fluorescent protein tags went through different post-translational processing, causing the GFP-tagged receptor to be correctly localized, but the brighter fluorescent protein tag caused receptor mislocalization. Conclusion Sometimes it seems easy to apply published reagents or methods to your own experiments. What is less discussed is the danger of it. In my past three years of training as a cell biologist, I have come to appreciate the complexity of biology and the delicacy of proteins and cells. It seems that we never have the full picture of how cells function. We can help ourselves by taking cautionary steps, understanding no reagent is guaranteed, and making sure there is minimal perturbation to the subject-of-interest.
Author: Danko Antolovic
The Broken Workplace
Prominent journals of popular science have lately seen a spate of articles about the horrors of the academic-scientific work environment: harassment, bullying, personal burnout, and theoverall “toxic” atmosphere of research groups. The discussion usually proposes remedies like harassment-awareness seminars, anti-bullying efforts of various kinds, and general exhortations toward greater “collegiality.” What should we make of all that? Well, as scientists, people of enlightenment and reason, we know that understanding the cause is the first step in addressing a problem. And if we look honestly at the situation, we see two distinct but related causes staring us in the face: competition for resources and a rigid professional hierarchy. Competing for Resources Academic science is consumed with the competition for grant money. Funds are necessary to do the work that generates personal credentials, such as publications and academic rank, and these credentials are then used to justify the next round of funding. Researchers have little choice but to follow this cycle if they want to stay in the game. Since the money is always tight, people look for cheap resources to exploit, usually lower down in the hierarchy. Graduate students—and sometimes even undergraduates—are routinely put under pressure to crank out publishable work, even though they are still only apprentices in their field and, in most cases, cannot be reasonably expected to make meaningful research contributions. The obvious goal of this pressure is to add to their advisors’ quota of published results, to be submitted with the next grant application. Graduate students also serve as a reservoir of inexpensive teaching labor for their university. Junior faculty, on the other hand, are an important source of outside money for their institution, money which is usually discreetly called “extramural funding,” and which confirms the (desirable) status of the institution as a research university. Proven ability to secure outside money is an absolute must for faculty hirings and promotions, and a typical school appropriates and manages a sizable portion of this money as research operating expenses. As a junior prof once told me: “You are expected to raise your own salary and the salaries of a few other people as well.” In this environment, there are no colleagues in the old-fashioned sense, only rivals. I have seen people in research groups deliberately obfuscate presentation of their current work to colleagues, for fear of getting scooped. My years as a university IT professional have made me keenly aware of how touchy researchers are about their IT privacy. They are not worried about hackers: they are worried about the guy in the office next door. And in my years as a researcher, I worried about the same thing. The Academic Totem Pole As for the hierarchy, all workplaces are hierarchical, but the academic hierarchy is different. At a small college at which I worked, an undergraduate student once literally wept in my office, relating the insulting conduct of a faculty member who had considerable say over her undergraduate thesis. What was I to say? I knew that the injury to her dignity would have to go unrequited, unless she was prepared to endanger her upcoming graduation by making noise about it. I advised her to rise above the insults, and to understand that that is how things are. What is a graduate student to do about an advisor who casually demeans students, demands servility of them, or worse? A grad student in a typical program is committed to a particular research project, guided by a particular advisor with expertise on the subject; the student has invested several years in this work and depends on the advisor’s help with the next career step. A mid-stream program change entails great disruption and a waste of effort. What is a junior faculty to do but grovel before his tenure committee members? Tenure opportunity is a rare, once-in-a-lifetime commodity in the academic world, and rare is the soul who will barter it away for some personal dignity. In ordinary employment, it is possible to walk away from a bad boss. Even highly skilled professionals’ commitment of effort and responsibility usually does not extend past the current quarter, and the price of defiance is a temporary loss of income, which can be regained elsewhere, along with a continued successful career. In academia , a scientific professional is locked into successive multi-year career commitments, in which changes of course are very costly and second chances as good as nonexistent; he/she is dependent on the mercies of the superiors, with little meaningful recourse. Surprised at the abuse? We should be surprised that we don’t hear more about it. Healing the workplace What is there to do, indeed? The causes of this misery are structural: the academic-scientific work environment is awful because of the way the scientific community is funded and organized, and well-meaning superficial remedies will have no effect. Once the sensitivity training seminars have been attended, and the human-relations consultants have departed, things will invariably revert to the old order, dictated by the need for money and by the vanities of human nature. The problem can only be addressed at its source. The first source, the unbridled short-term competition, is harmful in more ways than one: apart from making life miserable, it also diminishes the depth and quality of the science that comes out of it. It would be a worthwhilestructural reform to begin treating the scientific enterprise as a public good, akin to public education, road-building and the like, and subjecting its funding to public consensus and oversight [4]. This would replace the current grant-chasing bazaar with long-term public commitments to projects that are fewer in numbers but of greater public value; it would give researchers a relief from the endless funding race, and to their efforts it would give a steady direction and a sense of value beyond promoting their individual careers. The second factor, the abusiveness of the hierarchy, is a harder thing to address: it is rooted in some unpleasant traits of human nature, traits which everyone possesses to a degree, and those on top merely have a freer hand in expressing them. As a practical measure, introduction of labor laws and enforceable standards of conduct, tailored to address the academic environment, would be helpful in stemming excess and abuse. In that vein, it is heartening to see attempts at unionizing among the graduate students at some universities. Lastly, we should not deceive ourselves: healing the broken workplace of the scientist requires reforming the broken way science is done in our time, nothing less. Reforms will be resisted, as they always are, by those who fear change, and by those who stand to lose some perks in the process. But we, the scientists, must remind ourselves — and each other — that true scientific inquiry seeks knowledge that is more important than our professional creds, knowledge that makes human life better. By reclaiming that ideal, we will practice better, happier, more fulfilling science again.
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