Author: Staff Page 1 of 3

Storytelling for Scientists

On November 4, 2020

Written By: Sydney Wyatt

Edited By: Emily Cartwright

“Everyone can relate to stories.” – Chris Anderson, TED Talks

Storytelling is essential in scientific communication: we are always told to “tell a story with the data” in papers, posters and presentations. There are many methods for storytelling (see this resource), but I’ll focus on my two favorite methods—the throughline and “And, But, Therefore” (“ABT”). As an example, I’ll use a very simplified hero’s journey and workshop my research using the two methods:

The hero’s journey: The protagonist lived in a peaceful and happy world but a problem arose, therefore she set out on a journey to find a solution.

My research: I study the role of fibroblast growth factor signaling in ovary and testis development in zebrafish.

Method 1: The throughline

When I think of forming a story, be it a blog post or a scientific poster, I tend to use the idea of a throughline, or narrative arc. It can also be considered the “point” of the story and narrowed down into one sentence; you can find examples here for Harry Potter and The Sorcerer’s Stone and The Lord of the Rings. A throughline for my research might be: fibroblast growth factor signaling is implicated in ovarian cancer cell proliferation, thus it may have a proliferative role in normal development. The throughline connects all the elements in a story—the protagonist to the problem to the journey to the solution—just as the elements of a poster or paper connect all the data.

We’re trained to write in a throughline manner: introduction, methods, data/results and conclusion. However, we as scientists don’t usually communicate verbally with a throughline. Instead we tend to throw data at an audience, like lab-mates in a lab meeting, and expect the audience to “get it.” There needs to be context for the audience to care about the problem and thus understand the journey. Why would an audience care about fibroblast growth factor signaling? I need to explain that it’s increasingly detected in ovarian cancer for them to care about my project exploring its normal role in development.

A throughline can have other elements that contribute to it, like branches on a tree as explained by Chris Anderson, author of TED Talks: The Official TED Guide to Public Speaking. One such element is the anecdote, which is useful in a presentation to relate to the audience. For instance, I might have had a close family member with ovarian cancer and I could share some of their story; the audience can relate to me on this topic and will care more about my research in zebrafish. I don’t need to share the anecdote, but it adds flavor to the presentation. You might do this naturally in a casual lab meeting by inserting commentary on how well the methods are going. I highly recommend reading the book for more details.

Method 2: “ABT”

Narrative is extremely important in storytelling, as explained in the throughline method above. Randy Olson, author of Don’t Be Such a Scientist, developed the And, But, Therefore (ABT) method for developing a narrative. It goes like this:

And: The protagonist lived in a peaceful AND happy world. Applied to my work: fibroblast growth factor signaling has a function in many developmental contexts AND has been well studied in contexts such as limb development. This serves as the introduction to the work being communicated. What’s known about the field? Why will the audience care about the work?

But: The protagonist lived in a peaceful and happy world BUT a problem arose. Fibroblast growth factors signaling is important in development BUT we don’t know what role it is playing in ovary and testis development. The “but” introduces the problem the research addresses. It also leads into the research question (is this signaling pathway promoting proliferation or differentiation?) and the hypothesis (it promotes proliferation).

Therefore: The protagonist lived in a peaceful and happy world but a problem arose, THEREFORE she set out on a journey to find a solution. Fibroblast growth factor signaling is important in development, but we don’t know its role in ovary and testis development; THEREFORE we conducted research to investigate our hypothesized role. There’s a lot to pack into the “therefore” segment of a paper or talk. It includes your results, methods, discussion and conclusion. For a more in-depth review of this book check out this article. I also highly recommend the book itself, which includes an application of this method to a poster presentation.

This article’s throughline and ABT are very similar: storytelling is an important component of successful communication, but it’s challenging in a scientific context, therefore I’ll share some common methods of story development.

There is no single correct way to develop a story, and these are just my two favorite methods. I invite you to explore the resources below to discover your favorite storytelling elements, but be wary of trying to fit in too many elements at once. Practice using different elements in different settings. A throughline might be most appropriate for a paper, but the “ABT” method may be better for a poster presentation or elevator talk. As always, practice and get feedback from your peers!

Want to practice with UCD BioScope? Pitch us an article at ucdbioscope@gmail.com.

Additional resources:

Science Says’ storytelling and pitch workshops
The Open Notebook (TON) has a wealth of information on many aspects of science writing.
The National Association of Science Writers (NASW) has many resources on pitching and publishing science stories as well as professional development programs.
The Council for the Advancement of Science Writing (CASW) frequently collaborates with NASW to put together the annual Science Writers conference.

TED Talks: The Official TED Guide to Public Speaking by Chris Anderson

Don’t Be Such a Scientist by Randy Olson

You Don’t Have to Be a Monk to Meditate

By Staff

On September 23, 2020

In scientist_2.0, scientist_2.0_wellness

Anxiety, depression, insomnia — we all experience stress in one form or another and often on a daily basis. Most of us would like to think we’d do anything to diminish these hurdles to happiness, though it’s likely you’ve heard much praise for meditation yet never committed to giving the practice a proper go.

Perhaps you feel meditation is more effort than it’s worth, or that you’ll never master the skill because your mind is the kind that never rests. However, meditation is not meant to be complicated, nor does it have to be time consuming.

In her Nature Career Column article titled Building a meditation routine for a more productive, creative and happier scientific life, Ana Pineda, PhD shows us how simple meditation can be, offering four easy tips to begin practicing mindfulness meditation routinely in a way that’s achievable for everyone.

Scientists like Dr. Pineda are part of the growing number of individuals discovering mindfulness meditation as a free and uncomplicated way of alleviating stress and boosting productivity, focus, and creativity. If you haven’t tried mindful meditation yet or gave up too quickly on it once before, perhaps it’s time to give the practice an honest shot.

Stay healthy. Stay thirsty.

Nina Cueva

Resource suggestion made by: Yulong Liu

Edited by: Sydney Wyatt

Internet Accountability

By Staff

On September 15, 2020

In main_pub

Written by: Devan Murphy

Edited by: Jennifer Baily

Due to the pandemic, most of us are spending more time in front of our screens. Honestly, I spend a lot more time on social media than I used to, and it has affected my mental health. No, it isn’t the dreaded FOMO (fear of missing out). It’s the posts from some of my friends and family that have shattered my perception of the people I thought I knew. As I scroll, I see an accumulation of conspiracy theories about COVID, unwillingness to help protect others by wearing a mask in public, and little empathy or consideration for the essential workers and medical professionals putting their life on the line while we sit at home. Although the internet is a valuable tool with a wealth of information and a method for connecting people, it can also be used for the complete opposite—disseminating falsehoods and driving a wedge between communities.

This weighs heavy on my mind and heart as people who helped raise me and shape who I am today share and legitimize misinformed views on the pandemic. But the information they insist on propagating results in behavior that goes against the very values I learned growing up. To see them posting harmful opinions and incorrect information feels like an attack on my profession. As a student in the Veterinary Student Training Program, I reside at an interface between the medical and basic science fields. To me, this situation is similar to clients who come into the clinic, ignore your professional opinion, and insist on telling you how to do your job because Dr. Google diagnosed their pet’s ailments for you. In the light of COVID, research scientists are now getting a taste of this frustration dealing with a population that is either ignorant or belligerently dismissive of facts (although climate change scientists have known this pain for a while now).

I do understand how the public could be confused. There is SO MUCH information out there, but this is what we deal with in science all the time. And as graduate students, I think we are exceptionally good at updating our point of view when we receive new data. I remember a conversation with a family member about grocery bags. He was annoyed about paper bags being brought back into fashion. It went something like this:

I don’t understand. We used to use paper bags, then they told us not to cut down trees, so we all switched to plastic. Now, everything is “Plastic is bad, plastic is ruining this environment.” So, which is it? We are supposed to go back to killing trees?

I tried to explain that as we get new information, we need to reimagine our behaviors. It is natural for scientists to understand that nothing is simple. There are always things we don’t know; we live on the frontier of the known and undiscovered. As we find new information and uncover confounding variables, we build them into our understanding or understand when to reject them. I wish it was easy as a superhero movie, where the bad guy is easily identifiable. But that’s not the real world. It is messy and problems are multifactorial, and clear straightforward solutions rarely exist. But here is the irony, in this situation, a common enemy does exist! Coronavirus. So, with a clear threat in sight, why are some people insistent on defying health experts instead unifying to defeat the pandemic?

Initially, who knew what to do? Wear a mask, don’t wear a mask? And unfortunately, with government leaders not always being the most reliable sources, downplaying the severity of the problem and being slow to take action, it can be very confusing for someone watching the news to know what actions to take. However, now it is clear this virus is very contagious, deadly, and masks help prevent transmission. Therefore, perpetuating misinformation and bashing public health guidelines is a safety concern.

So, as graduate students, a community versed in critical thinking and evaluating primary literature, is it part of our job to combat misinformation online? Is it our place? And what internal conflict does this pose to call out our family members or friends? Interestingly, I wanted a career in science because I thought it was the unbiased pursuit of facts, untainted by the subjectivity of the humanities. Why deal with people when numbers don’t lie. But numbers can lie. In the worst case, they are purposely manipulated(1), but even in the best of circumstances, statistics without context mean nothing. And without placing these numbers in the proper context, it is easy to misdirect the audience. As recent events have made perfectly clear, science is not devoid of these conflicts. Our science is funded by taxpayers to help the public, therefore, getting involved to make science interpretable and usable to the public is implied in that paycheck.

Leaders and officials seem to be catching up on the relevance of internet accountability. The United Nations started an initiative to provide reliable information about COVID(2) and some social media sites like Twitter began fact checking posts(3). But to do this, you need to critique the information. Scientists do this all the time with peer review, disclosing conflicts of interest, and discussing the limitations of their work. However, it takes time to go through and fight/debunk all of the misinformation. In contrast, it takes NO effort to make stuff up to support a false narrative. I’m lucky enough to still have my job, and I honestly don’t have the time to refute all the misinformation I come across. To some extent, it must be the responsibility of the individual to self-educate. Again, there is a wealth of information online.

While I strive to stress the importance of accountability online, I acknowledge that this may not be an entirely safe conversation as people feel attacked when you dispute their worldview. So much of science has been tied to politics, which becomes emotional quickly. Being rejected or cut off by loved ones may not be an option. But if possible, in the way that personally works best for you (1-on-1 conversations, public sharing of valid resources, etc.), I think we have some responsibility as a science community to stop the spread of misinformation. That doesn’t mean everyone will listen, but letting this information spread unchallenged, like the virus, is dangerous.

(For more information, about spotting misinformation and fighting it, check out Fleming’s article (4) )

Florida and Georgia facing scrutiny for their Covid-19 data reporting – CNN. https://www.cnn.com/2020/05/20/us/florida-georgia-covid-19-test-data/index.html.
Online training as a weapon to fight the new coronavirus. https://www.who.int/news-room/detail/07-02-2020-online-training-as-a-weapon-to-fight-the-new-coronavirus.
Twitter fact-checks tweets linking 5G and coronavirus – Business Insider. https://www.businessinsider.com/twitter-factchecks-tweets-5g-coronavirus-2020-6.
Fleming, N. Coronavirus misinformation, and how scientists can help to fight it. Nature 583, 155–156 (2020).

Far From Home

By Staff

On September 8, 2020

In main_pub

Written by: Ellen Osborn

Edited by: Ross Wohlgemuth

Many of us leave home in order to attend college. It is a modern-American rite of passage when we throw what physical items we care about into a suitcase and leave the place and people that, up until that point, were our whole world. And yet, the physical separation that is a defining part of the university experience is rapidly overshadowed by the emotional separation formed as we build social networks and expose ourselves to new perspectives. The learning and expanding that occurs at university can reinforce values learned at home, strengthening core convictions about how life works and what matters most. It can also deconstruct, maybe even shatter, parts of you. After a few years, the physical distance separating you from home can still be overcome by modern day travel, but the psychological distance that develops can feel increasingly unbridgeable. In my case, my childhood home is not too far from where I attend university, but the separation I feel from the community that raised me is devastating.

I was a difficult kid. I got into fights in school, did not make or keep friends easily and was aggressively tomboyish. I vividly remember laying on my bedroom floor as a nine-year-old, thinking that I hated everyone around me and did not understand why I was alive. My mom, the exceptional person that she is, decided to homeschool me during those rough years. We joined a small, Christian fundamentalist homeschool group, and through the years, I grew into a completely different person. The people in my new community shaped me; due to their efforts, I began caring for others, making friends and appreciating the value of my life. Because of this personal transformation, I feel a deep sense of love and gratitude toward my home community. I understand their actions were well-intentioned, and the lessons they explicitly and implicitly taught me came from a place of love and concern. In addition to the lessons of love and kindness, they taught me that homosexuality, abortion, evolution and even liberalism were evils in this world. They taught me that a woman’s ultimate purpose in life is to stay pure, marry and have many children. They taught me that California public universities would rob me of my faith and scientists could not be trusted. I believed most of what I was taught and arrived at community college with my guard firmly up.

Despite the anti-science views entrenched in my home community, I was drawn to science. After only a few classes, science no longer seemed to be the amoral machine of secularization whose design was to deceive. Rather, I saw science to be a study of the complex beauty of the world around us. Continuing my education as a transfer student in a biology major, I learned more about nature’s detailed complexity and what I learned was not always compatible with my first worldview. LGBTQ+ people are not immoral; women are research powerhouses in academia; evolution is supported by evidence.

Parts of my worldview needed to be reconstructed in order to accommodate my newly acquired relationships and knowledge. The longer I lived in my new community of friends, classmates and mentors, the more lessons from my upbringing were replaced by lessons from my adult life. This exchange did not occur because I was swept up in the groupthink of an institution; instead, I was developing love and empathy for the people who shared with me their values and beliefs and challenged the narrowness of my worldview. I still loved my home community, but our vantage points were no longer the same. In addition to the physical distance separating us, there was a growing psychological distance created by every lesson I no longer believed.

The 2016 election revealed the immediate consequences of the psychological separation from my home. People I loved and respected were unreservedly saying things I once agreed with but now considered to be wrong. Vitriol and outright insults were leveled by both of my old and new communities. I could feel my conscience pushing me to be a bridge between the divide, but I felt like an imposter in both places. I had, in a way, abandoned my home community both physically and psychologically, and yet I still felt loyal to those people and understood their anger. Ultimately, my feelings of self-doubt and anxiety associated with sticking even a toe into the maelstrom of outrage relegated me to the position of a conflicted observer. Finishing college in a post-2016 world and becoming a graduate student in a STEM field, my observer status persisted.

The events of this year have forced me to reevaluate my role in this divide. Rampant misinformation and prejudice are reinforced by closed social networks. Opponents, including scientists and peers I respect, degrade and publicly reprove these groups, the effect of which is to further feed the machine of mistrust and distaste. As an observer, it seems as if I am already conceding defeat: anything I say will be immediately drowned out by the outrage.

But I do not want to be characterized by defeat. What if I can connect, listen and engage with just one person on the other side, and lessen the outrage they feel? What would happen if we gently correct misinformation when we see it and offer evidence that breaks the cycle of confirmation bias? Could we slowly build bridges that narrow the psychological separation between divided communities? I am just beginning to grasp the enormity of America’s culture war between science and fundamentalism, so these questions could be a result of my naiveté. When I doubt my ability to bridge the gap, I think of Barack Obama, who overcame the institutions framed against him to become the first Black president of the United States, and his quote: “Change will not come if we wait for some other person or some other time. We are the ones we’ve been waiting for. We are the change that we seek.”

It is painful to parse out the consequences of psychological separations from the people we love, and even more so to take the next steps to try to bridge that separation. Fortunately, it is not just one person’s job to build that bridge; I’ve had many encouraging conversations with other graduate students that are reaching out to their home communities in small but meaningful ways. Even if that is all we can do now, it is a start.

To be continued.

The Molecular Biologist’s (Virtual) Toolbox

By Staff

On August 11, 2020

In scientist_2.0, scientist_2.0_toolsforsuccess

There are many useful tools out there to assist you with plasmid mapping, primer design, and DNA sequence analysis, so many that it can be difficult to keep track of them all. Thankfully, Addgene has made it simple to find the exact tools you need with their Early Career Research Toolbox, which lists most, if not all, of the most useful free research tools available online for molecular biologists. In it, you’ll find tools to help you view, edit, and create plasmids, manipulate DNA sequences, identify and compare DNA and protein sequences to free online databases, facilitate cloning ligation reaction calculations, and more.

Even if you’re certain you already have all the tools you’ll ever use, I advise you to give Addgene’s toolbox a peek. You may just find a new application you didn’t know you needed.

May your thirst for knowledge never be quenched,

Nina Cueva

Resource suggestion made by: Yulong Liu

Edited by: Yulong Liu and Sydney Wyatt

It’s time to get deep (TMS).

By Staff

On August 4, 2020

In main_pub

Written by Jen Baily

Edited by Anna Feitzinger

Illustration by Sydney Wyatt

As I sit with earplugs in my ears, a tight velcro cap and a firmly secured helmet on my head, my right hand and right eye twitch of their own accord while the magnetic field creates a drumroll sensation two inches into my skull. It only lasts three seconds, but repeats over twenty minutes until my session is complete. This will continue every day for a month, then twice a week for two months.

As someone with drug-resistant major depressive disorder (MDD), there are few options available to treat my symptoms, especially after being on the maximum doses of 5 different medications over the last few years. Electroconvulsive therapy (ECT), colloquially known as shock therapy, is often used as a last resort; however, it can cause severe memory loss and brain damage. Anecdotally, I’ve known friends that have undergone ECT who were never the same, which took it off the table for me. It wasn’t until meeting a psychiatrist to manage my medications that I learned about deep transcranial magnetic stimulation (dTMS), and how it is a non-invasive procedure for which I was a good candidate.

From the paragraphs above, as well as the name dTMS, you probably get the idea that dTMS is a deep, skull-penetrating magnetic pulse. How can this be used specifically to treat depression? The idea behind dTMS is to use this magnetic field to affect neurons, which act as conductors.

In 1985, Anthony Barker and his associates produced the first transcranial magnetic stimulation (TMS) device. It was based on Faraday’s discovery in 1881, where a magnetic field was created by running electricity through a coil. By rapidly switching the magnetic field’s intensity or direction, you can depolarize neurons in a specific region of the brain. Though not fully fleshed out, it is thought that increasing the neural activity in the mood center of the brain, the dorsolateral prefrontal cortex (DLPFC), may be the mechanism by which dTMS alleviates symptoms of depression.

The treatment targets the DLPFC on the right side of your head. The psychiatrist or technician finds the DLPFC by applying magnetic pulses until your hands begin to twitch, indicating the magnetic fields have reached the motor cortex. This allows the doctors to position the helmet containing the magnets over the DLPFC and to induce the firing of neurons in the area. dTMS is akin to Transcutaneous Electrical Nerve Stimulation (TENS) machine, except dTMS is specialized to stimulate the brain while TENS is inTENded (pun) to reduce pain. Nevertheless, the principle of manipulating the nervous system to the benefit of the patient remains the same. The neural activity caused by the dTMS magnets increases expression of brain derived growth factor (BDGF), increased neural outgrowth and connectivity in rats (Paus, 2011), and showed a major elevation in mood of patients relative to a placebo treatment during clinical trials (Yates, 2016). BDGF accomplishes these tasks due to its role in development, maturation, and maintenance of neurons.

By increasing the activity of neurons in the brain regions typically affected in patients with MDD, a burst of growth is thought to follow the acute/intense phase of treatment, when a patient is going in every day. During the second phase, where a patient is treated a few times a week, the activity is thought to be maintained while the brain adjusts. Relative to previous models of the TMS technology, deep TMS has an excitingly high “remission rate of 32.6 in active deep TMS (vs 14.6 sham treatment)” (Levkovitz, 2015). Remission of MDD is typically thought to be a significant decrease in depressive symptoms for longer than 4-6 months (Frank, 1991). While this may seem like a low number, for someone suffering from depression, any reduction in symptoms can be helpful, and full remission of symptoms can allow someone to function normally. For the third of patients who’ve never felt relief, this is life-changing.

After extensive studies on rats and clinical trials on humans, the FDA approved dTMS use for patients who had failed 2 or more medications during their current episode of depression. Because dTMS is not a medication, simply a locally applied magnetic field, it is without the usual side effects such as “weight gain, sexual dysfunction, nausea, tremors, dry mouth, diarrhea, headaches, constipation, sweating, sleepiness or anxiety” that are associated with antidepressant use (History of dTMS). What’s wonderful, in my opinion, is that the patient can drive to and from their appointment. There are minimal side effects that usually dissolve shortly after a treatment session. Apart from the super magnets being quite noisy, the strangeness of the feeling itself, and occasionally scalp tenderness, it really is an amazing option for patients with drug-resistant MDD.

If dTMS is such a wonder “cure” for depression and anxiety related disorders, 1) why haven’t more people heard of it and 2) why don’t more people utilize this technology? To address question one, I’ll quote my lovely psychiatrist, “stigma.” There is a certain stigma associated with a daily treatment regime, especially one that requires transportation to a clinic. Though effective, it is a new technology and can often be lumped together with ECT in the public eye, which can be a traumatic experience for patients. To address question two, dTMS is very expensive. UC student health insurance is quite good for mental health services, but even then, I had to fail out of 5 medications and rate at a specific level of depressive symptoms prior to any coverage for almost a year. Failing out of medications involved either severe side effects or lack of effect for 16 weeks of treatment. If the insurance company doesn’t think you’ve gone hard enough for long enough, they can request that you take higher doses of medication prior to approval. All this is associated with the side effects mentioned previously, and during this time the patient is suffering. Additionally, a patient may be suffering to the point of suicidal ideation, but is functional enough to score below the required threshold on a PHQ-9 form. If a patient battling with depression must be their own advocate while on heavy medications and experiencing symptoms, getting to a place where dTMS is possible can be difficult. However, things are starting to change for the better.

As dTMS becomes a more mainstream treatment option, more and more patients are seeking it out to ameliorate their symptoms. Along with the patients themselves feeling better, those in their lives are able to notice improvements. My own partner told me that I was able to carry a conversation for significantly longer after a month of treatment relative to my depressive episode. As more and more people notice the impact that this treatment has on their loved ones, word will spread. Additionally, within the past 10 years, mental health stigma has significantly decreased. Now, I can openly talk about my own experience with minimal impact to my career prospects, and am still viewed as a functional and contributing member to my community.

In learning about dTMS for my own sake, I was amazed by the scientific literature behind it. The technology brings together physics and physicians, neuroscientists and patients. Through their creative and thorough research, hope has been brought to many suffering with MDD, myself included. If you or someone you know has struggled with a severe depressive episode, perhaps now is a good time to discuss dTMS with your physician or other new technologies as treatment options. And always remember, reach out if you need help. You’ll be surprised by how many people and how many treatments out there can help.

On campus services – UCD specific

https://leadership.ucdavis.edu/strategic-plan/task-forces/mental-health

Individual counseling
Couples counseling
Group therapy
Skills groups
Case management
Career counseling
Outreach to the campus community

They only work if you use them.

Partial Hospitalization and Intensive Outpatient Programs

Group therapy at a hospital location, often using cognitive behavioral therapy, with access to on-call psychiatrist and nurse.

National Suicide Prevention Lifeline

We can all help prevent suicide. The Lifeline provides 24/7, free and confidential support for people in distress, prevention and crisis resources for you or your loved ones, and best practices for professionals.

Online Chat – Lifeline

1-800-273-8255

“Warm Line” – Talk to trained listeners before a crisis: Visit http://www.warmline.org/ to find the number for your area.

Talk to trained listeners over text: https://www.crisistextline.org/

References

http://www.brainefit.net/history-of-tms.html

Yates E, Balu G. Deep Transcranial Magnetic Stimulation: A Promising Drug-Free Treatment Modality in the Treatment of Chronic Low Back Pain. Del Med J. 2016;88(3):90‐92.

Johnson, Mark. “Transcutaneous Electrical Nerve Stimulation: Mechanisms, Clinical Application and Evidence.” Reviews in pain vol. 1,1 (2007): 7-11. doi:10.1177/204946370700100103

Levkovitz, Y., Isserles, M., Padberg, F., Lisanby, S. H., Bystritsky, A., Xia, G., … Zangen, A. (2015). Efficacy and safety of deep transcranial magnetic stimulation for major depression: a prospective multicenter randomized controlled trial. World psychiatry : official journal of the World Psychiatric Association (WPA), 14(1), 64–73. doi:10.1002/wps.20199

Tomáš Paus Manuel A. Castro‐Alamancos Michael Petrides (2011). Cortico‐cortical connectivity of the human mid‐dorsolateral frontal cortex and its modulation by repetitive transcranial magnetic stimulation. European Journal of Neuroscience. 14(8), 1405-1411. https://doi.org/10.1046/j.0953-816x.2001.01757.x

Frank E, Prien RF, Jarrett RB, Keller MB, Kupfer DJ, Lavori PW, Rush AJ, Weissman MM. Conceptualization and rationale for consensus definitions of terms in major depressive disorder. Remission, recovery, relapse, and recurrence. Arch Gen Psychiatry. 1991 Sep; 48(9):851-5.

In memory of Syndey Brenner: his part of the discovery of messenger RNA

By Staff

On July 7, 2020

In main_pub

Written by: Hongyan Hao

Edited by: Ellen Osborn

All biology undergraduates learn the central dogma: DNA makes RNA and RNA makes protein. However, not long ago, this dogma was intensely debated because it was unclear if DNA or protein contained the genetic material of the cell. The famous double helix model opened the door to molecular biology in 1953. But it took an additional eight years to discover the messenger RNA. Sydney Brenner, who shared the 2002 Nobel Prize in Physiology or Medicine, was a key traveler in this long journey.

Portrait photograph of Sydney Brenner, c. 1960s,
Copyright: MRC Laboratory of Molecular Biology

As described in his autobiography, My life in Science, Brenner thought about how genetic information guides protein synthesis even before he saw the double helix model in April 1953 at Cambridge. Inspired by the similar step size of nucleic acid (3.5 angstrom units) and amino acids (3.3 angstrom units) pointed out in William Astbury’s 1947 paper, Brenner developed his “pet theory” that amino acids join together at the same time nucleic acid strands are synthesized. At the time, people knew that DNA sequences defined proteins, but it was not clear whether there was an intermediate molecule between DNA and protein. With the discovery that protein synthesis occurs at ribosomes, it was largely assumed that the intermediate was the ribosomal RNA (rRNA). However, some people were skeptical about this. One reason for this skepticism was that in bacteria, the ratio of the amount of G+C to A+T in DNA varied a lot between bacteria species, while in rRNA the variation was trivial.

Another concern was what Brenner called the “paradox of the prodigious rate of protein synthesis.” While working with bacteriophages at Cambridge, Brenner and Francis Crick observed that after phage infection, 70% of protein made in the infected bacteria was the phage head protein instead of the bacteria protein. If rRNA is the intermediate for protein synthesis, a significant increase of new rRNA should be observed. However, there was no detectable rRNA synthesis. In 1956, Elliot Volkin and Lazarus Astrachan discovered that a small amount of short-lived RNA resembles the phage DNA in base composition rather than the bacterial DNA after phage infection, however, they were kind of focused on the idea that these new RNA could be the precursor of phage DNA.

Four years later, the secret of the mysterious Volkin-Astrachan RNA was uncovered in Brenner’s living room. It was during an informal meeting of a small group of scientists, including Crick and François Jacob from Institut Pasteur in France. Jacob described the new findings from the famous Pardee, Jacob and Monod (PaJaMo) mating experiment. Normally, bacteria synthesize galactosidase in a medium containing lactose. However, the lac- mutant cannot digest lactose until the gene that encodes the galactosidase is transferred into the cell. Galactosidase synthesis is extremely rapid, happening within minutes. Interestingly, when they let the bacteria produce galactosidase for some minutes and then destroyed the transferred DNA, galactosidase synthesis stopped immediately. These results ruled out the possibility of any stable intermediate like rRNA because if the intermediate were stable, galactosidase synthesis should have continued for a while after the gene was removed. Upon hearing Jacob’s description, suddenly, Brenner got excited and shouted to Crick, “Volkin-Astrachan; information intermediate; it’s short-lived; a short-lived intermediate! It must be! Look at the way it turns over in phage!”

The next step was to plan experiments testing whether the short-lived RNA was the intermediate messenger that guides protein synthesis. If Brenner’s hypothesis was correct, then the new RNA intermediate synthesized after phage infection should be associated with the old bacterial ribosomes.To do this, they needed a way to distinguish between the ‘new’ and ‘old’ ribosomes. Lucky for them, Matthew Meselson and Frank Stahl at California Institute of Technology (Caltech) developed the density gradient centrifugation experiment and successfully separated the isotope N15-labeled DNA from the N14 DNA in a caesium chloride solution. The RNA intermediate experiment could use this approach to label bacterial ribosomes with isotopes before phage infection and resuspended in the medium without isotopes right after infection, which would make the old ribosomes heavier than the new ribosomes and therefore distinguishable by density gradient centrifugation.

Jacob and Brenner went to Matt Meselson’s lab in California the following summer to test their new hypothesis. The experiment that followed was, as described by Brenner himself, a “hilarious story”. The experiment itself was complex, isotopes were expensive, samples needed to be spun in the centrifuges for nearly 20 hours or more, and the centrifuges were unreliable. And they only had three weeks! The first problem Jacob and Brenner encountered was that the ribosomes were not stable and dissociated during sedimentation in the centrifuge. They tried to troubleshoot, but to no avail. They even thought of purifying ribosomes from Dead Sea bacteria because they already live in a high salt environment and might be more tolerant of the high concentration of caesium chloride. Unfortunately, their phage couldn’t infect the Dead Sea bacteria.

Frustrated and tired, they went to a nearby beach to, in Brenner’s own words, “rest their weary souls”. Jacob recalled this time in his autobiography: “There we were, collapsed on the sand, stranded in the sunlight like beached whales. My head felt empty. Growing, knitting his heavy eyebrows, with a nasty look, Sydney gazed at the horizon without saying a word.” Lying on the beach, it occurred to Brenner that magnesium stabilizes the ribosomes and the high caesium could displace the magnesium, making the ribosomes unstable! They ran back to the lab and set up their last-chance experiment of three samples with higher magnesium concentrations. During the chaos, Jacob dropped the radioactive phosphate in the water bath and the centrifuge broke down in the middle of the experiment! Luckily, they were able to borrow a centrifuge from a neighboring lab. Nervously, Brenner carried the rotor with the tubes to the cold room. He walked there because the elevator would shake the tubes, destroying the gradient he had worked so hard to create. In the end, they managed to finish the experiment and showed that the new radioactive RNA peaked at the same position with the old ribosomes! Later, these results were published in Nature in 1961, along with the discovery from James Watson’s lab that a fraction of rapidly labeled RNA of different sizes were associated with the ribosome active site (where protein synthesis happens). That same month, the term “messenger RNA” and it’s possible role in gene regulation was discussed in Jacob and Monod’s review article in Journal of Molecular Biology.

Even today, the exploration of messenger RNA never ends. I’m fascinated with how the friendship between scientists, critical thinking, effective communication, and collaboration all contributed to the discovery of messenger RNA. When we hear stories about scientific discoveries, it often sounds like a genius just appeared and came up with an idea that changed the world. But Sydney Brenner’s story shows that it’s not that simple. Scientists can make wrong hypotheses, create naive models and misinterpret results. Sometimes, experiments won’t work; sometimes people tell you not to try an experiment because it is unlikely to work; sometimes you get weird results; sometimes people question and laugh at your hypothesis. But sometimes you make fascinating discoveries. Sydney Brenner passed away in April 2019 at the age of 92. Brenner’s obsession with science, creative thinking, open mindedness, and persistent pursuit of answers will continue to inspire scientists like myself.

Sources:

Brenner, Sydney. My Life in Science. London, 2001.
Hernandez, Victoria, “The Meselson-Stahl Experiment (1957–1958), by Matthew Meselson and Franklin Stahl”. Embryo Project Encyclopedia (2017-04-18). ISSN: 1940-5030 http://embryo.asu.edu/handle/10776/11481
Meselson, Matthew, and Franklin W. Stahl. “The replication of DNA in Escherichia coli.” Proceedings of the national academy of sciences 44.7 (1958): 671-682.
Brenner, Sydney, François Jacob, and Matthew Meselson. “An unstable intermediate carrying information from genes to ribosomes for protein synthesis.” Nature 190.4776 (1961): 576-581.
Gros, François, et al. “Unstable ribonucleic acid revealed by pulse labelling of Escherichia coli.” Nature 190.4776 (1961): 581-585.
Morange, Michel. “What history tells us XLV. The ‘instability’ of messenger RNA.” Journal of biosciences 43.2 (2018): 229-233.
Cobb, Matthew. “Who discovered messenger RNA?.” Current Biology 25.13 (2015): R526-R532.

In Light of Recent Events: What We Can Do

By Staff

On July 7, 2020

In scientist_2.0_activism

Between the disproportionate burden of the coronavirus on BIPOC (Black, Indigenous, People of Color) and the most recent murders of innocent Black Americans by police across the nation, the true scope and impact of racial inequality in the United States has become painfully and undeniably evident.

A majority of Americans now recognize that in order to end the sanctioned murder of innocent Black Americans at the hands of the police, it is imperative not only to insist on dramatic police reformation, but to deliberately change the culture that has long permitted systemic racism to undermine and subdue BIPOC.

So what can we do as busy graduate students to actively effect lasting change? Individually, we can educate ourselves on the subject and work to deconstruct our own biases, conscious or otherwise, that continue to allow racism to persist in our society; as academics, we can further address the roots of racial inequalities by promoting the increased involvement of BIPOC in STEM disciplines.

One such opportunity involves becoming a National Summer Undergraduate Research Project (NSURP) mentor of microbial science for a BIPOC undergraduate student this upcoming July. If you apply now, you can make NSURP’s second window of month-long research projects taking place mid-July to mid-August. Projects will be done remotely this year because of COVID-19, and although this means traditional lab work will not be an option, it has created the unique opportunity to mentor a student regardless of their institution, city, or country!

Go to https://nsurp.org for more information on how to become a mentor.

May your thirst for knowledge never be quenched,

Nina

Resource suggestion made by Will Louie

Edited by Anna Feitzinger and Mikaela Louie

Organize Space and Time to Keep Sane in Isolation (Or Otherwise)

By Staff

On June 1, 2020

In scientist_2.0_toolsforsuccess

Like most (if not all) of us here at Bioscope, you may be struggling with how to remain productive while doing primarily everything in isolation. You may have even found yourself attending classes, working from home, and watching Netflix, all from the same, sunken, spot on your bed more times than you’re pleased to admit. Although this may have worked for the first few months of quarantine, by now you’ve probably noticed how unsustainable this habit really is.

In the Youtube video “Lockdown Productivity: Spaceship You,” CGP Grey illustrates how living in such a disorganized, unstructured manner undermines our ability to maintain our individual “spaceships” by impairing our mental and physical well-being necessary for its operation. Learn the simple, though effective ways of keeping your sanity and maximizing your productivity when operating in a finite area by making the most of your space and blocking out areas to work, sleep, exercise, and couch (apparently couch is now a verb).

I truly believe these techniques are helpful no matter how small your functional area and regardless of our current coronavirus pandemic. I hope you think so too.

May your thirst for knowledge never be quenched, friends,

Nina

Resource suggestion made by: Yulong Liu

Edited by: Yulong Liu and Keith Fraga

How to Make Your Zoom Presentation Pop

By Staff

On June 1, 2020

In main_pub

Written by: Tess Gibson

Edited by: Sharon Lee

Viewers join one by one, and presentation time is about to begin. But how do you grab the audience’s attention when they’re miles away? Here are some tips to make your Zoom presentation stick out from the crowd.

Use eye contact

The nature of online presentations allows you to make every audience member feel you are speaking directly to them. However, this only works if you’re looking directly into the camera. Though it may not come naturally, you should look into the little green light as much as possible so your audience can sense that you are present despite your distance.

Emphasize your verbs

No one wants to listen to a monotone lecture, and there’s even less incentive over Zoom, when you can turn off your video and snooze away. When you give a presentation online, a monotone lecture may even make it appear that you’re reading off of a script. A sure way to add interest is putting action into your verbs. Try writing out your hook and highlighting your verbs. For example, one should ask “how do we stop cancer?” instead of mumbling “how do we stop cancer?”. Use this to practice bringing life into your presentation and then transition to practice without your script. Adding a little extra excitement and inflection to your verbs grabs the attention of the audience and keeps them engaged with wherever you’re taking them next.

Use animations

Most people know to try to limit the amount of words on a slide, but what do you replace them with? Animations! Using animations is a great way to “show” your audience rather than “tell.” You want the audience focused on your visuals, not reading a complete sentence off of your slide. Start with the basics by animating circles or arrows to appear on command as a way to highlight portions of your images. Then, take it up a notch by animating images to appear one after another using timing controls to achieve a sequentially animated talk that seems almost more like a movie than a presentation. If building multiple animations into one slide is daunting, you can also use multiple slides to add or remove images with the same effect.

Keep it aesthetically pleasing

Nothing is more off-putting than a glaring typo or an unintentional shift in font halfway through a presentation. On Zoom, these tiny errors have an even greater impact because a majority of the screen is your slide. Proof-reading your presentation is a simple but key step in the preparation process. Some common issues to look for are…

Typos
Font size, type, or color shift
Lack of continuity (e.g. using complete sentences in some cases and not others)
Poor quality images
Mislabeled graphs and tables

If you include it, talk about it

It’s great to have figures, but if you don’t explain them, no one in the audience will know what they mean. Be sure to explain your axes, what the figure tells you, and how it relates to your main point. If the results are not conclusive, discuss that too. Try using the laser pointer feature in place of your mouse to explain specific parts of your figures as you talk about them.

Squeeze your butt

Lastly, squeeze your butt! That’s right, go ahead and try it! This is a silly but useful trick to start off your presentation right. Plant your feet, straighten your back, and tighten your behind. Don’t worry, you don’t have to maintain this posture for your entire presentation. Feel free to relax and move your arms. This is just to start you off with a feeling of confidence and strength.

With these tips in mind, your audience will need a magnifying glass because they’ll want to zoom in on your presentation!