By Monika Buczek
In the past decade, the human gut microbiome has has been implicated in many diseases, including but not limited to food allergies, celiac disease, diabetes, and certain autoimmune diseases as well as weight gain and obesity. However, study of the gut microbiome is slowed by a lack of adequate model systems in which to observe changes to both host and gut flora under certain conditions. Recently however, the nematode C. elegans has been identified as a possible model for studying the effect of the microbiome on metabolism- and subsequently how those changes to metabolism affect certain disease states.
Caenorhabditis elegans has long been used a research model organism for aging, autophagy, apoptosis and even diabetes, but the nematode may have a further function in determining the role of the gut microbiome in host metabolism. This tiny worm uses environmental cues to determine if the time is right to reproduce, or if conditions call for entering a type of dormancy called Dauer Diapause, a long-term stress-resistant stage in the C. elegans life cycle. Environmental temperature, population density, availability of food as well as chemical signals from pheromones and, as we are currently learning, bacteria are all important factors that help determine the worm’s choice between active reproduction and Dauer. However, until recently, the exact effect of bacterial genes on Dauer wasn’t quite clear.
A team of researchers from the Buck Institute for Research on Aging have identified a slew of gene mutations in E. coli K-12 that enhance the transition of C. elegans into Dauer state, sometimes resulting in increased life span. Specifically, the group identified certain E. coli mutants that increase the transition of the C. elegans insulin-like receptor mutant, daf-2, into Dauer.
Insulin signaling is well-conserved across the animal kingdom. While humans have several insulin receptors, the DAF-2 protein is the only member of the insulin receptor family in C. elegans. It holds 35% identity in protein sequence to the human insulin receptor, 34% to the human IGF-1 receptor and and 33% to human insulin. Human insulin and orthologous insulin-like genes in C. elegans inhibit DAF-2 receptors in C. elegans, which leads to activation of Dauer stage. The daf-2 mutant similarly arrests C. elegans development and redirects the worm’s life cycle into Dauer, which increases longevity and prevents reproductive maturity. The goal of this study was ultimately to observe which E.coli single gene mutations and their associated changes in metabolites, increased the rate at which both wild type and daf-2 mutant C. elegans entered into Dauer.
The Buck Institute group screened around 4,000 strains of E. coli from the Keio Collection, a collection of single-gene deletions of all nonessential genes in Escherichia coli K-12.Each strain in this collection has only one gene knocked out at a time.The Buck institute group fed the E.coli Keio mutants to various C. elegans strains and the group identified 56 genes that enhance Dauer formation in daf-2 mutants. Certain E. coli mutants, such as the cya mutant, which is deficient in the ability to produce cyclic AMP, were even able to increase the lifespan of wild type C. elegans as well as the daf-2 mutant counterpart. This work is important because it demonstrates how even one bacterial gene mutation is capable of altering the physiology of the host organism.
The group believes studying the bacterial-host interactions may be applicable to host-microbiome interactions in other species. The function of certain bacteria has been well described in several human diseases including obesity,liver diseases, metabolic syndrome, autoimmune disorders like food allergies, and diabetes.
A particular application of this research is elucidating how the human gut microbiome affects nutrient uptake and alters the phenotypes of certain genetic mutations. The authors state “interaction between bacteria and C. elegans can be used to understand conserved signals that are likely to play a role in host-microbiome interactions in humans which may influence diseases like Type II diabetes and obesity.”
All in all, a new and easily tractable model for human microbiome research and disease is a very welcome addition to the vast and quickly evolving field of research.
Monika Buczek is a PhD candidate in molecular biology and an associate writer for the American Society for Microbiology.
Author Contact: firstname.lastname@example.org
Editor: Julija Hmeljak
By Julija Hmeljak
I’m not going to lie; I am no computational biologist. Even though anything “omics” has been all the rage in cancer research for the past decade, I used to sit firmly on the “Genomics Papers Are Boring” train. But the day came when, out of necessity, I started reading papers on genomics, and the subject itself blew my little mind. Since cancer research occupies approximately 45 % of my time, cancer genomics papers are the ones I have the strongest feelings about. And where do these feelings come from? Mostly they stem from my postdoctoral project, which focuses on characterizing the biological consequences of specific mutations in cancer.
Image Credit: Holly Gramazio (Attribution-NonCommercial 2.0 Generic (CC BY-NC 2.0) lincese to reproduce the image)
Yet, reading scientific papers is just as much part of research as conducting experiments. Sometimes, reading scientific papers to answer questions for my own research leads me to recreational reading outside my specific field. That’s exactly what this roundup is meant to be – a roster of cancer genomics papers that might be outside your reading list, but are so good that you shouldn’t miss them. I evaluated each paper’s scientific merit, study design, and presentation style to compile my top 8 cancer genomics papers of 2016, ranked as follows:
Bueno et al., Nat Gen (2016); 48: 407-416. DOI: 10.1038/ng.3520
The first entry in my list is a “classic” descriptive genomics paper. Despite seemingly lacking some of the panache that other papers on this list have, this paper is a Big Deal for mesothelioma researchers, as it provides the largest molecular profiling study for this difficult organ-lining cancer type. Their correlations of molecular signatures with tumor subtypes are especially fascinating, as they provide some necessary understanding of molecular processes that drive phenotypes with a high impact on disease prognosis.
Kumar, Coleman et al., Nat Med (2016); 22: 369-378; DOI: 10.1038/nm.4053
This paper elegantly tackles one of the scourges of oncology: tumor heterogeneity and its most impactful consequence—recurrence after therapeutic intervention. To identify if molecular drivers are shared among individual tumor nodules within the same individual, the authors sequenced multiple prostate tumors and compared mutational, transcriptional, and copy number landscapes within and between individual patients. The paper’s main conclusion was that major genetic drivers identified in a single metastasis can provide a reasonably good basis for extrapolation to other tumors within an individual prostate cancer patient.
Alexandrov et al., Science (2016); 354: 618-622; DOI: 10.1126/science.aag0299
A massive one – the sheer size of the endeavor would warrant this paper a spot on the list, but the authors managed to take it further. They analyzed more than 5000 samples of cancer types typically linked with tobacco smoking. Comparing cases by smoking status allowed the authors to identify the effects of tobacco smoke on DNA sequence and methylation pattern alterations, and, importantly, evaluate the contributions of different mutational signatures to the genomic landscape in smokers and non-smokers. Interestingly, they found that tobacco smoke affects DNA sequence much more significantly than it affects methylation patterns.
Behjati, Gundem et al., Nat Comm (2016); 7: 12605; DOI: 10.1038/ncomms12605
Radiation is one of the most frequently used therapeutic approaches for cancer patients. Secondary cancers due to ionizing radiation are a well-recognized risk, although radiation’s exact effects on DNA had not previously been mapped. This paper investigates the mutational processes that occur in secondary, radiation-induced cancers and identifies two distinct mutational signatures of ionizing radiation. These signatures might help explain the mutagenic and carcinogenic potential of ionizing radiation, either in causing primary or secondary cancers.
Marcotte et al., Cell (2016); 164: 293-309; DOI: 10.1016/j.cell.2015.11.062
A smooth integration of dropout RNAi screens, which are designed to identify genes whose expression is of fundamental importance for survival of a cell line, on a whopping 77 breast cancer cell lines and large-scale genomics to identify both general and context-dependent genes essential to breast cancer progression, drug sensitivities, and resistance mechanisms. The strongest value of this paper is in its using a large panel of cell lines to minimize potential bias that can arise from using heterogeneous cell lines.
Piscuoglio et al., Clin Cancer Res (2016); 22: 4045-56; DOI: 10.1158/1078-0532.CCR-15-2840
Second breast cancer entry on the list. This time, the work was done in humans. Male humans. Breast cancer’s devastating frequency in female patients is common knowledge, but males are at risk, too. Due to its rarity, comprehensive studies are difficult to carry out, and the paucity of studies affects treatment strategies, which are usually extrapolated from results of studies on female patients. This comparative study of male versus female luminal breast cancer relied on a targeted sequencing panel that identified a distinct repertoire of genomic alterations specific to male breast tumors.
Notta et al., Nature (2016); 538: 378-382; DOI: 10.1038/nature19823
Pancreatic adenocarcinoma is a uniformly fatal cancer that was classically regarded to have a step-wise development trajectory demarcated by distinct acquired DNA sequence alterations, which result in a progressively more malignant disease. This paper challenges this classic linear model and provides insight into the divergent evolution of both the precursor and tumor lesion lineages.
Sulak et al., eLIFE (2016): 5:e11994; DOI: 10.7554/eLife.11994
A cheeky one, but irresistible. Spoiler: ELEPHANTS! In all seriousness, this very interesting and, may I say endearing, study analyzed the mechanisms of “Peto’s Paradox” – the lack of apparent correlation between body size and cancer risk. The authors confirmed that “Peto’s Paradox” is grounded in genomic amplifications of the TP53 locus and the evolutionary co-occurrence of this amplification with increasing body size in the Proboscidean lineage.
Disclaimer: this list is subjective. There have been numerous remarkable achievements in cancer genomics this year, and there are many more exciting papers within our reach. The subject of cancer genomics is constantly evolving, with fascinating advances made every day. Here’s to reading about those advances in 2017 and onwards!
Julija Hmeljak is a postdoctoral fellow at Memorial Sloan Kettering Cancer Center in New York City.
Editors: Tristan Fehr and Yue Liu
By Melissa A. Deri, PhD
This panel was organized by NYC Science Communication, with the support from The Office of Career Planning and Professional Development at The Graduate Center, The City University of New York, in order to provide an overview of medical communications, a look at what the job entails, and how to approach the current career landscape. The moderator—Preshita Gadkari, a doctoral candidate at Rutgers—led the discussion to focus on how young scientists could break into the industry and what they could expect in the medical writing profession.
Photographer: Xinjun Zhang
Christina Hughes, PhD Senior Director, Medical and Scientific Affairs, Medical Exchange International, New York
Qing Zhou, PhD, ELS Scientific Communications Scientist, Cook Research Incorporated, West Lafayette
Lashon Pringle, PhD Medical Director, Healthcare Consultancy Group, New York
Leighland Feinman, PhD Scientific Affairs Associate & Medical Writer, AXON Communications, New York
Typical Career Path
As with most career panels, when you ask a group of people about the typical path of how they got where they are today, you find that there is, in fact, no such thing as a typical path. Some panelists pursued a medical writing career straight from graduate school, another panelist after years as a postdoc. Some chose it as a way to apply science, others to satisfy a love of writing. Nonetheless, the common link between the four individuals was an enthusiasm for science paired with a dissatisfaction with the current reality of “doing science” as a career researcher. These were people who wanted to talk and write and think about science, but did not feel the pull of being the one holding the pipette, much less the one applying for grants to justify the expense of the pipette. They enjoyed the challenge of problem solving, but wanted more satisfying work where hard work led to tangible outcomes. Secondly, no one’s path was entirely solitary, as each panelist highlighted leveraging networks and connections to get into the field. The overwhelming recommendation for someone who wants to enter into the field is to make connections with current medical writers to find medical writing opportunities.
Practical Job Overview
Just as there are varied paths to get into medical writing, there are many versions of what medical writing can entail. Three of the panels work for medical communication agencies that work with outside clients, largely private pharmaceutical companies, but Qing Zhou works internally for a medical device company. Writers can work on publications, promotional materials, educational materials, and even strategy, helping clients to figure out what they want and need. Most medical writers work within teams and juggle a number of clients and projects all at once. The job is inherently social in that you will need to work with clients, doctors, statisticians, scientists, and business people. Thus, effective communication skills for various technical and lay audiences are key. Additionally, the critical thinking, problem solving, and analytical skills learned while completing PhD are constantly needed. Leighland Feinman described medical writing as a way “get paid to think … and come up with intriguing answers to problems.”
Career Outlook & Potential
The panel emphasized that the field of medical communications is an active and thriving area for PhDs to consider as an alternative to academia. Specifically, there are a number of medical communication companies with offices in New York (those discussed are listed in Table 1) nearly all of which are actively hiring PhDs straight from graduate school. The consensus was that while experience is always helpful, a postdoc does not hold any direct advantage to being hired as a medical writer. The greatest advantage for an applicant is to have a network connection within the field. One way Qing Zhou suggested to make these connections was by getting involved with the American Medical Writers Association.
Table 1. Selected Medical Communications Companies in New York
|AXON Communications||BGB||Flywheel Partners|
|Grey Healthcare Group||Healthcare Consultancy Group||Imprint Publications|
|Medical Exchange International|
Suggested starting salaries ranged from $60-85k and the panelists emphasized that there is ample room for upward mobility even within the first few years. Within the industry, there is significant fluidity and recruiters are always looking to bring experienced writers into other companies. Thus, within a company, promotions are common in order to stay competitive. In addition to career advancement, this fluidity offers the opportunity to shape your career and focus on the aspects of medical writing you enjoy. For example, Lashon Pringle found she especially liked strategizing and opted to take a position where she could equally write and strategize.
The panel was overwhelmingly positive, emphasizing that medical communications is an enjoyable field offering engaging work and a respectable salary. Most importantly, it is a field where there are actually job openings where PhDs are valued and sought after. A final note of encouragement for young scientists near or at the end of their PhD work was given by Christina Hughes: “You are absolutely employable and don’t think you’re not.”
Melissa Deri is a PhD radiochemist and science educator in New York City.
Editor: Monika Buczek
By Yue Liu
For any aspiring medical writer, the American Medical Writers Association (AMWA) can provide valuable professional resources and volunteering opportunities. In this article, Qing Zhou, PhD, ELS, shares how educational and volunteering experiences at AMWA both catalyzed her professional growth and facilitated her transition from a graduate student and bench scientist to a ten-year medical writing veteran.
Interviewee: Qing Zhou, PhD, ELS
Scientific Communications Scientist at Cook Research Incorporated; Treasurer and President-Elect of the AMWA New York Metro Chapter
“Volunteering is a great way to show what kind of person you are and to build up professional relationships.”
What is your current position?
My current title is Scientific Communications Scientist at a medical device company. I oversee a program of scientific publications for more than ten active clinical studies. I collaborate with study investigators, clinical scientists, statisticians, and product engineers to publish research findings on innovative medical devices and technologies.
What is your educational background? How did you find your way in medical writing?
I grew up in China and received my PhD in Molecular Pharmacology from Purdue University in West Lafayette, Indiana. In graduate school, besides the extensive writing requirements for my doctoral studies, I also took several writing courses, including a professional writing class from the English Department. Through these writing experiences, I learned how to write research grants, scientific papers, essays, memos, and even manuals. I realized that I really enjoyed writing, so I decided to explore science communications as a career option. I researched the field of medical writing and joined the AMWA Indiana Chapter. Joining AMWA was the best decision I made for my professional development.
Why was joining AMWA the best decision for your professional development? Were the educational resources of AMWA helpful in your career transition?
I submitted an essay on ethics in scientific publication and won the Indiana Chapter student scholarship in 2007, which enabled me to attend the chapter’s annual conference. After this first taste of medical writing, I also applied for the AMWA student scholarship at the national level and I got it! This scholarship funded my trip to the AMWA annual conference and gave me the opportunity to take three educational workshops of my choice. This experience opened my eyes to the broad field of medical writing and gave me a better understanding of this profession. I created a diverse portfolio for my job search and quickly landed a job in medical writing.
After you landed a job in medical writing, what skills did you find essential in your work?
To be successful at work, it is crucial to possess not only writing and technical skills but also soft skills, such as leadership, time management, project management, and interpersonal communication skills. Volunteering at AMWA has been integral in developing my soft skills over the years.
What was your first volunteer experience?
AMWA gave me a lot, and I wanted to pay it back and forward. After becoming a full-time medical writer, I embarked on the journey of volunteering at AMWA. My first volunteering experience was at the AMWA Indiana Chapter, where I served as a newsletter editor for five years. I planned each newsletter with the chapter board, coordinated content, conducted interviews, and wrote articles myself.
Did you also volunteer at the national level?
Yes. From 2010 to 2012, I served as the Chair of the AMWA Annual Conference Student Scholarship Committee. From 2012 to 2014, I served as the Chair of the AMWA Medical Book Awards Committee in the public category. As a past recipient of the student scholarship, I understood the weight of the award. As someone who loves books but was new to book reviewing, I wanted to make sure the judging process was balanced and fair. Therefore, on both committees, I built strong teams of judges, who cooperated to make the review processes efficient and objective. I really enjoyed these experiences. It was my pleasure to help more students break into this career, and it was my honor to contribute to the excellence of medical writing.
How did these volunteer experiences at AMWA develop your soft skills?
As a newsletter editor, I had the opportunity to work with many other chapter board members during planning, writing, editing, and proofreading newsletters. As the chair for the award committees, I assembled a strong panel of judges, established rapport, and provided leadership. For example, at the Book Awards Committee, where the judging process spanned 3 months, I ensured that every judge was making progress in a timely manner. Also, toward the end of the process, I coordinated discussions among the judges to reach a consensus. Everyone was busy. I learned to prioritize. As a result, I enhanced my time management skills and learned to work more efficiently.
Did those volunteer experiences expand your professional network?
Absolutely. Volunteering is a great way to show what kind of person you are and to build up professional relationships. You get to interact with people whom you normally wouldn’t. When you work in a team, there is a mutual understanding; you can show that you are responsible and reliable in a supportive environment.
What is your suggestion for people interested in volunteering at AMWA?
Start from something small—at a local chapter, for example—and take responsibilities that match your commitment. At the national level, you can complete a volunteer interest form. You don’t have to be an excellent writer or a great leader to start volunteering. Everyone has unique strengths and talents. Everyone can bring in unique perspectives and energy. As long as you have a passion for medical writing, the desire to improve yourself, and the willingness to contribute to the profession, any type of volunteering will be a great start.
A key part of NYC Science Communication (NYCSciComm)’s mission is to guide STEM PhD students to navigate career options in science communication. If you are looking for a career with an ideal work-life balance, a stimulating environment with exposure to cutting-edge medical advancements, and competitive salaries, medical writing might be a perfect career option for you.
Success in medical writing calls for a set of communication and leadership skills often outside the scope of STEM doctoral education. To gain experience and build these skills, you can volunteer at professional organizations like NYCSciComm or AMWA. At NYCSciComm, volunteering provides a platform for you to sharpen writing skills, build up your portfolio, and expand your professional network. If you are interested in writing blogs and/or volunteering for us, please contact us at email@example.com.
Acknowledgement: This article was part of the AMWA Empire State-Metro New York Chapter Newsletter in August 2016 and appears first to the public on the NYCSciComm website. The author would like to thank the AMWA-NY Chapter board and the Editorial Board of NYCSciComm for their valuable feedback.