All posts by Kayla Gross

Top Techniques: Single-Cell RNA Sequencing

Image from Papalexi E & Satija R, Single-cell RNA sequencing to explore immune cell heterogeneity. Nat Rev Immun (2017).

As scientists ask increasingly focused and nuanced questions regarding cellular biology, the technology required to answer such questions must also become more focused and nuanced. In the last decade, we have already seen several significant paradigm shifts in how to process data in a high-throughput manner, especially for genomic and transcriptomic analyses. Microarrays gave way to next-generation sequencing, and now next-generation sequencing has moved past bulk sample analysis and onto a new frontier: single cell RNA sequencing (scRNA-Seq). First published in 2009, this technique has gained increasing traction in the last three years due to increased accessibility and decreased cost.

So, what is scRNA-Seq?

As the name suggests, this technique obtains gene expression profiles of individual cells for analysis, as opposed to comparing averaged gene expression signals between bulk samples of cells.  

When and/or why should I use scRNA-Seq compared to bulk RNA-Seq? What are its advantages and disadvantages?

The ability to examine transcriptional changes between individual cells uniquely allows researchers to define rare cell populations, to identify heterogeneity within cell populations, to investigate cell population dynamics in depth over time, or to interrogate nuances of cell signaling pathways—all at high resolution. The increased specificity and subtlety given by single-cell sequencing data benefits, for example, developmental biologists who seek to elucidate cell lineage dynamics of organ formation and function, or cancer biologists who may be searching for rare stem cell populations within tumor samples.

Practically, scRNA-Seq often requires far less input material than traditional bulk RNA-Seq (~103-104 cells per biological sample, on average). The trade-off for this downsizing advantage, however, is because of the lower input, there is often more noise in the output data that requires additional filtering. Also, as with any rising star high-throughput technique, standardized pipelines for bioinformatics processing of the raw output data are still being finalized and formalized. As the same type of growing pains occurred when bulk RNA-Seq rose to prominence, no doubt a more final consensus will also eventually be reached for scRNA-Seq.

What platforms are used for scRNA-Seq?  

The three most current and common workflows to isolate single cells for sequencing are by microplates, microfluidics, or droplets.

Microplate-based single cell isolation is carried out by laser capture of cells, for example by FACS, into wells of microplates. This approach is useful if there are known surface markers that can be used to separate cell populations of interest. It also provides the opportunity to image the plate and ensure that enough cells were isolated and that it was truly a single cell isolation. Reagents for lysing, reverse transcribing, and preparing libraries are then added to individual wells to prepare samples for sequencing.   

Microfluidics-based single cell isolation consists of a chip with a maze of miniature lanes that contain traps, which each catch a single cell as the bulk cell mixture is flowed through. Once cells are caught within the traps, reagents for each step of the sample preparation process (lysis, reverse transcription, library preparation) are flowed through the chip lanes, pushing the cell contents and subsequent intermediate materials into various chambers for preparation, followed by harvesting the final material for sequencing.

Droplet-based single cell isolation also uses microfluidics but instead of traps it involves encapsulating, within a single droplet of lysis buffer, (1) a single cell and (2) a bead linked to microparticles, which are the reagents necessary for sample preparation. The advantage of this approach is that a barcode can be assigned to the microparticles on each bead, and thus all transcripts from a single cell will be marked with the same barcode. This aspect allows pooling of prepared samples for sequencing (decreasing cost) as the cell-specific barcodes then can be used to map transcripts back to their cell of origin.

The other significant consideration for designing scRNA-Seq experiments is what sequencing method to use. Full-length sequencing provides read coverage of entire transcripts, whereas tag-based sequencing involves capture of only one end of transcripts. While the former approach allows for improved mapping ability and isoform expression analyses, the latter allows for addition of short barcodes (Unique Molecular Identifiers, UMIs) onto transcripts that assist in reducing noise and bias during data processing.    

So, which platform should­ I use?

As with most advanced techniques, determining which platform to use depends on the biological question being asked. A microplate-based platform does not accommodate high throughput analyses but does allow for specificity in what types of cells are being analyzed. So, for example, it would be a good choice for investigating gene expression changes within a rare population of cells. It also does not require particularly specialized equipment (beyond a FACS machine) and thus is a relevant choice for researchers without access to more sophisticated options. Microfluidics-based platforms are capable of more throughput than microplate-based while retaining sensitivity, but they are more expensive. Finally, droplet-based platforms provide the greatest amount of throughput but are not as sensitive. Thus, they are most appropriate for elucidating cell population composition and/or dynamics within complex tissues.

How can my scRNA-Seq data be processed, and is it different than bulk mRNA-Seq data processing?

Performing computational analysis on scRNA-Seq data follows a similar pipeline as bulk RNA-Seq, though there are specific considerations required for scRNA-Seq data processing, especially during later stages of the pipeline. One of the major considerations is significant cell-to-cell discrepancies in expression values for individual genes. This effect occurs because each cell represents a unique sequencing library, which introduces additional technical error that could confound results when comparing cell-specific (and therefore library-specific) results. This effect can be mitigated during data processing by additional normalization and correction steps, which are included in most of the publicly available scRNA-Seq processing pipelines.

Finally, the types of interpretations drawn from scRNA-Seq experiments are also technique-specific and question-dependent. Common analyses of scRNA-Seq data include clustering, psuedotime, and differential expression. While clustering is done with bulk RNA-Seq data, clustering scRNA-Seq data allows for assessing relationships between cell populations at higher resolution. This aspect is advantageous for investigating complex tissues—such as the brain—as well as for identifying rare cell populations. Given the large sizes of scRNA-Seq data sets, performing clustering of scRNA-Seq often requires dimensionality reduction (i.e. PCA or t-SNE) to make the data less noisy as well as easier to visualize. By coupling clustering results along with differential expression data, identifying gene markers for novel or rare populations is made easier. Psuedotime analysis is particularly useful for scRNA-Seq experiments investigating stages of differentiation within a tissue. Using statistical modeling paired with data reflecting a time course (for example, various developmental stages of a tissue), this analytical method tracks the transcriptional evolution of each cell and computationally orders them into a timeline of sorts, thus providing information relevant for determining lineages and differentiation states of cells in greater detail.  

Where can I do scRNA-Seq in Boston?  

Tufts Genomics Core here at Sackler has a Fluidigm C1 machine (microfluidics). Harvard Medical School (HMS) has several options for single-cell sequencing platforms. HMS Biopolymers Core also has a Fluidigm C1 system that is available for use on a for-fee, self-serve basis after training, with reagents purchased and samples prepared by the individual, as well as a 10X machine (droplet). HMS Single-Cell Core has a inDrop machine (droplet) that includes for-fee full service with faculty consultation.

What is the future for scRNA-Seq?

Bettering the way in which samples are processed and data is analyzed is a priority for scRNA-Seq experts. Specifically, ongoing work seeks to improve library preparation and sequencing efficiency. The programs used to process scRNA-Seq data are also still in flux so as to provide better normalization and correction tools for increasingly accurate data. On a larger scale, developing technology to analyze other biological aspects (genomics, epigenomics, transcriptomics) at the single cell level is of high interest, especially when considering how powerful combining these other forms of single-cell analysis with transcriptomics could be for understanding both normal and disease biology.

Resources:

  1. scRNA-Seq software packages: https://github.com/seandavi/awesome-single-cell
  2. Review of bioinformatics and computational aspects of scRNA_Seq: https://www.frontiersin.org/articles/10.3389/fgene.2016.00163/full
  3. Practical technique review: https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-017-0467-4
  4. Start-to-finish detailed instructions on scRNA-Seq: https://hemberg-lab.github.io/scRNA.seq.course/biological-analysis.html

New Sackler leadership envisions training to career excellence

The beginning of this academic year has seen a shift in the leadership of the Sackler school with the retirement of both the Dean & the Associate Dean. Dr. Naomi Rosenberg’s decision to retire from her role as the Dean of Sackler after 13 years of dedicated service was received with a mixture of surprise and trepidation, which was compounded by Associate Dean Kathryn Lange’s retirement decision around the same time. The dynamic duo left large shoes to fill and the search committee spent the summer choosing candidates who would have the school and its constituents’ best interests in mind. To that end, Daniel Jay, Ph.D., a faculty member of the Developmental, Chemical & Molecular Biology department, and Daniel Volchok, Ed.D., previously the Assistant Dean for Graduate Student Life at Northeastern University, were chosen to fill the positions of the Dean and Associate Dean, respectively. Both of these individuals bring their extensive experiences to the table. Dean Jay has mentored numerous graduate students and has served as the post-doc officer for the school prior to his appointment as the Dean, and Assoc. Dean Volchok has worked with both undergraduates and graduate students across multiple disciplines that range from medical schools to business schools.

For Dean Jay, a fortuitously timed conference on graduate education solidified his commitment to throw his hat in the ring, while Assoc. Dean Volchok found that beginning his position simultaneously with a new Dean was a wonderful opportunity to build a fresh vision for Sackler from the ground up. Aside from similar serendipitous timing, Jay and Volchok also developed convergent objectives for how to keep Sackler and its associated graduate programs a competitive academic institution. Of particular interest regarding these new goals is that they grew directly out of interactions with students.

“In my interview, with the students I met with, they all talked about career,” Volchok recalled. “It was very important to the students. It turned out they were right…career focus is part of the life here.”

Jay states that their new mission for Sackler is one of “training to career excellence”, which encourages high distinction not only at the bench for students, but also in less traditionally academic contexts, such as in the boardroom or at the news desk. “The reason for that,” Jay explained, “is that 80% of our trainees go on to careers beyond academia…and we need to train all of those individuals in addition to the small number that do go on in academia to compete, to excel, and to lead in areas of whatever their chosen career passion.”

Both Jay and Volchok believe that trainees are the key to Sackler’s success. To highlight the importance of student leadership, Jay mentions that “extracurricular programs, that didn’t exist 10 years ago, were developed by student leadership such as the GSC [Graduate Student Council], TBBC [Tufts Biomedical Business Club] and the PDA [Postdoctoral Association].” They both want to see this trend to continue as they would like students to take ownership of their career choices and approach the Dean’s office with their needs and wants to ensure their success. Jay believes that “we will be stronger and better if we are willing to change with the times to provide what students require for success.” He is also less concerned that faculty may not be on board with non-traditional career choices. He believes that most faculty are not opposed to career choices outside of academia, and he stresses that research excellence is still the first priority for any trainee at the Sackler school and will not be compromised

In his twenty years at Tufts, Jay has watched, as well as aided, the trainee community forge extracurricular programs and initiatives to fulfill these alternative training needs, despite, and more aptly because of, the shortage of accessible resources. To build upon this foundation, this fall semester the Dean’s office launched two new trial initiatives: a drug development short course, taught by alumnus Stefan Gross, and career counseling services provided by Sarah Duncan. In addition, Volchok is currently working on developing a business skills course based on his experience in Northeastern’s business school; such action speaks to the fresh perspectives he brings to Sackler through his extensive and varied educational and administrative experience. While this type of career training will remain supplemental in the short-term, they plan to eventually incorporate such training directly into the infrastructure of Sackler. This integration will run the gamut from admissions to available curriculum, such as proposed course offerings focused on business or transferable skills (eg – team building, project management, etc.), school-facilitated industry internships that are integrated into a student’s research plan, and possibly a two-year biomedical Masters program that would incorporate training in both research and non-traditional science career development.

The majority of these programs will be accessible not just for graduate students but also for Tufts postdocs as well. Jay’s role as the post-doc officer for the school has made him very much aware of the bottleneck effect of the current academic job crisis that these postdocs face. Therefore, he has stressed that programs be made open to the whole Sackler community whenever possible. He also proudly mentions the success of the PDA, which organized around 70 events last year, and affirms his faith in trainee leaders to build career-related programs. Unfortunately, industry internships will not be open to postdocs, but Jay hopes to work with industry contacts to improve that situation.

The success of these programs and the new vision, according to Jay, will be evaluated by whether “graduates have an easier time finding their first job.” He mentions that he developed this milestone after his conversations with alumni who wished they had learned particular skills before entering the job market. In these conversations, he also discussed building more formal engagement between the alumni and the school, such as the possibility of alumni acting as adjunct professors to teach aforementioned short courses and the development of a biomedical research interest group. He affirms that he has had a positive reaction from the alumni who have also expressed interest in hosting/organizing events. He also mentions that alumni would definitely be a part of the new branding strategy now that the Dean’s office has developed its new mission. As a key component to executing these varied goals, Jay and Volchok have also established and seeded a new Sackler career development fund, dedicated to financing the programming to come out of this new mission.

Jay and Volchok aim to use their first year to launch programs that would serve as “trial balloons.” The school is “small, so [it is] easy to make changes”, according to latter, and therefore, they would like to test out which programs can be expanded upon in the long term. “This year will test the viability and utility of these short courses that can be used to build upon for longer term goals, and student engagement and participation will be crucial to seeing these initiatives succeed,” Jay elaborated. This last point seems to be critical to the new administration, as “feet on the ground”, as Jay put it, will be the litmus test for whether these initiatives continue. Both seemed confident that the students will indeed engage, given how proactive the trainee community has been about this topic in the past, and are ready and willing to listen to individual feedback.

“We’re of the size that we can make sure students are successful,” Volchok observed. “We can work with individual students when we need to. Students can feel like part of the community and not just a number.”

While a small student body has organizational advantages and new approaches can be tested easily without much bureaucratic repercussions, there are also disadvantages. The current funding climate, along with the fact that Sackler is surrounded by heavyweight schools with similar programs, has led to a dwindling number of students recruited to our programs every year. In the light of such events, concerns regarding the continuity of Sackler as a successful graduate school are bound to rise. However, both Jay and Volchok believe that their new mission of a strong emphasis on career development will help Sackler stand out amongst the other schools in the area.

“I view this as our route to success…how do we define ourselves in a very competitive environment,” Jay said. “If we dedicate ourselves wholeheartedly to this mission, we would, in some ways, distinguish ourselves so that we are competitive, so that a student may choose us because they seek this path toward career excellence. We have to find a way to be relevant…I think the combination of being in Boston, of being small and mobile–if we can do it, we set the standard for the rest of the country. So that is exciting to me, and that’s making a difference, and this is why I’ve taken this job.

Besides the strong emphasis on career development, the Dean’s office’s new mission also prioritizes community building both in and outside of Tufts. Jay mentions a great advantage that Sackler has by being surrounded by Medical, Dental and Nutrition schools, and being in the same university as a Veterinary school–all opening doors to an influx of opportunities for trainees and faculty to design their studies that could result in more collaboration within the school. As an example, he cites the Clinical & Translational Science Institute (CTSI) and their intentions of working more with the Sackler Basic Science programs (CTSI currently offers drop-in hours for statistics consultation and also offers a course on biostats, both of which are open to Sackler trainees). Jay is also looking forward to hearing individual programs’ changes to curriculum based on discussions between students and faculty mentors (CMDB is offering a bioinformatics class to its students after it was brought up in the program retreat). Additionally, Jay hopes to reach out to industry as well for more collaboration on various fronts.

Jay and Volchok are also tuned in to the social needs of the community to protect its members while reaching outside of their bubble. They are both advocates of the new student club Scientists Promoting Inclusive Excellence @ Sackler (SPINES), and stressed “increased awareness of diversity and inclusion” and building a tolerant community. In an effort to increase student engagement, Volchok has revised The Goods–a weekly digest of news, opportunities and events both on and off campus–delivered to the school community. He believes that “students have a good voice here” and are great resources on how the school and its environment can be improved. Both Jay and Volchok mentioned the need for more community outreach into middle schools, both in the Chinatown communities and the African-American communities in Roxbury. They would like the students to help with organizing and mentoring in these communities.

Of course, most of these ideas are still in the very early stages. “We’re at the very beginning of all this,” Jay said with a laugh. Even so, they seem to be off to a good start, as Jay and Volchok spent their first few weeks listening to the needs of the community before shaping their mission. Jay admits “…the level of concern and frustration of career path thing is here,” an issue frequently brought up by students in the past. Jay and Volchok are committed to listening to the needs of the trainees and helping them as much they can, but they also want the students to take ownership of their own career paths by being proactive. When asked what the students can do to help the Dean’s office, Volchok expresses his eagerness to work with students to improve their experience at Sackler. “Be open and honest with us. Come and tell us when things are going well. Come and tell us when things are not going well. If you have ideas and things we can do differently, let us know.”

An exciting new group, NEGWiSE, kicked off this summer with an Inaugural Retreat connecting New England area graduate women in science and engineering

by Siobhan McRee & Heather Tanner

There was an excited tension in the humid halls of Boston University the morning of August 19th, where women from eight institutions across New England were finally coming together under one roof. For months leading up to this day, representatives from each school spent many a late-night brainstorming, planning, and organizing, not just the Inaugural Retreat they were attending today, but the genesis of a new organization whose mission would be to unite, diversify, and advocate for women in science and engineering throughout New England. They had just founded NEGWiSE: New England Graduate Women in Science and Engineering.

The retreat kicked off with the keynote speaker: local entrepreneur, founder, and CEO of Seeding labs, Dr. Nina Dudnik. Her nonprofit company brings scientific equipment and training to underserved areas worldwide, and the theme of her talk was collective action. As she spoke, she acknowledged that tens of thousands of protesters were currently marching on the Boston Common to protest racism and hate speech, and many in the audience had cut their marches short to hear her speak. Protest signs littered the aisles as Nina pointed out that by taking the time to support fellow women here and now, when there were other pressing and important issues, strongly demonstrated the passion and dedication of everyone in the room. Continuing to echo the national conversation, Nina emphasized that the time for talking is over, and she urged, to many a nodding head, now we must act.  

Nina talked about her time as a graduate student at Harvard Medical School, where she overcame extreme gender imbalances to find mentors and advocates, and ultimately changed the demographics of her department to hire more women. She spoke of how we as women in science must work harder, be more productive, and walk a fine line to be just the right amount of outspoken but likable – feminine but firm. She said that often we, as women, do this with an apologetic meekness that we must shirk to accept full ownership of our accomplishments. Her advice: practice saying the words “My name is…and I am an expert in…”  because this is something we consistently feel shy about, regardless of our achievements or awards. But we can help each other do this too. Nina encouraged us to amplify each other’s voices; whether in meetings, in lab, or online, me must give and receive credit. We must also repeat, reinforce, and validate other women’s viewpoints so their voice, and our collective voices, can be heard. We can build an ‘old girl’s network’ of our own. This is a kind of power we can harness to act on, to affect change, and keep improving.

Nina reminded us that we as women are already working overtime; here we are choosing to spend our Saturday, not on the couch watching TV, but actively working to both question and improve the status quo, all the while standing in solidarity with other women. But as a new group, Nina stressed, it is important we distinguish ourselves, to find a niche among the multitude of women’s groups in the Boston area. As her keynote wrapped up, the room was uplifted with a common hope and strength. Nina put words to the thoughts we all had- that together we have the resources not just to talk but to act, and facilitate important and sustainable change.

Building off the groundwork laid by Nina, the next part of the retreat featured short presentations from each school about their GWiSE groups, where representatives from Tufts, Boston University, MIT, Northeastern, Harvard, Brown, Boston College, and Dartmouth all talked briefly about their strengths and resources, and how they could benefit from a consortium like NEGWiSE. While Tufts does not have a dedicated GWiSE group (yet!), the Tufts Mentoring Circles stood in to represent Tufts, and will also be supporting the development of a Tufts GWiSE group that’s currently in the making.

The bulk of the afternoon was dedicated to several “Breakout Sessions.” These focused discussions were brainstorming sessions on topics such as the organizational structure of NEGWiSE, the role of men, increasing diversity, outreach, and advocacy. Tufts’ own Dr. Ayanna Thomas, professor of Psychology, led the diversity discussion to brainstorm how NEGWiSE could facilitate enhancing diversity, both regarding incoming graduate student demographics and within high level graduate education positions. Likewise, discussion was held about how other GWiSE groups at other universities can help Universities such as Tufts to create their own internal GWiSE group.

However, one Breakout session that received a lot of traction was Advocacy. Attendees, added to the momentum started by Nina’s keynote speech through eager discussion of action items affecting graduate students and consideration on how NEGWiSE could implement change. Several issues rose to the top as important within the STEM graduate community, including parental leave policies, mental health, domestic violence, and student/advisor dynamics. In fact, NEGWiSE decided to take on resource gathering about parental leave policies for comparison across universities, with the goal of proposing a standard policy for graduate student parental leave that can be proposed directly to each administration. This timely issue is the first action item that NEGWiSE will be tackling, but it will not be the last. Through the breakout sessions, the mission of NEGWiSE was refined to include graduate student advocacy as a central tenant, especially for issues relating to women in STEM. It was strongly felt that NEGWiSE will distinguish itself among Boston area groups in this way, while also best serving the needs of multiple universities across New England.

But the retreat was not simply all work and no play; after the brainstorming was over, the fun began! Moving from the classrooms of BU to the BU Beach, attendees met and networked with each other over delicious BBQ. A scavenger hunt encouraged people to talk to each other. Attendees needed to find a person who fit each condition from a list. For instance, items included who had run a marathon or who likes Dunkin Donuts better than Starbucks. The first few people to find answers to all those questions won some NEGWiSE swag. A fun photo booth with props got everyone laughing, while a DJ spun tunes, and a Facebook friending frenzy ensued.

The Inaugural retreat introduced the framework and mission of NEGWiSE, a new group to connect, support, and advocate for graduate women in science and engineering. Soon the NEGWISE will hold their own elections for this year’s committee which will follow with many more activities which will be announced at Tufts. Likewise, the Medford and the downtown campus are negotiating our own GWiSE group. If you want to get involved with the Tufts GWiSE group that is forming and will partner and collaborate with NEGWiSE, please contact tuftsgwise@gmail.com.  Also, you can follow NEGWiSE on twitter @NE_GWISE or on Facebook at New England GWiSE

Library Roundup: A Review of Helpful Links, Tips, & Resources

Every month, librarian Laura Pavlech from the Hirsch Health Sciences Library helpfully provides us with invaluable tips and reminders about resources that are available to the graduate student population to help with their research and other academic needs. 

In appreciation for all of her hard work this past year, here is a look back at what she assembled for our use:

NOTES FROM THE LIBRARY

PUBMED TIP OF THE MONTH

Thanks again to Laura for assembling these wonderful aids!

 

New England Graduate Women in Science & Engineering Retreat, August 19th

NE GWiSE Inaugural Retreat!

New England Graduate Women in Science and Engineering (“N-E-G-wise”) is a new alliance between groups of graduate women in STEM from universities in Boston and across New England. We’re joining forces to address the issues facing graduate women in STEM. Join us for our first event, the NE GWiSE Inaugural Retreat, this summer! Details can be found below or at our website, https://negwise.wordpress.com .

Description: Come join us at NE GWiSE’s Inaugural Retreat- a day of connecting graduate women from different universities and collaborating to help make NE GWiSE an organization that can effectively address the issues we face and create change within our community.

We will start off the day being inspired by our opening keynote speaker (TBD). Next, we will have introductions by partner GWISE groups and breakout sessions to discuss how NE GWiSE will function. Finally, we’ll end the day with a scavenger hunt and BBQ social! This is a great opportunity to meet graduate women from different departments and universities, share best practices and recurring issues, and foster collaborations and friendships across the region. We hope to see you there!

Registration closes August 16th at 5pm so sign up now!

Date: Saturday, August 19th, 2017

Time: Registration is 12-1 pm, Opening Keynote starts at 1 pm, Event goes until ~7 pm

Location: BU College of Graduate Arts and Sciences and BU Beach

Coffee and snacks will be served throughout the event. Dress is casual.

 

 

GSC Committee & Club Updates: April 2017

Tufts Biomedical Business Club (TBBC)

from Aaron BernsteinCMP

Upcoming Events

TBBC Case Study Group: Mondays – 5-7PM, Jaharis 508

Practice solving cases, gain insight and tips, and learn more about the field of consulting.

TBBC Tufts Biomedical Alumni Speed Networking Night: Th Apr 13 — 6-8PM, Sackler 114

TBBC, in collaboration with the Office of Alumni Relations will be hosting a speed networking night! Meet fellow students and Tufts alumni who are working in the biomedical field from across all of Tufts campuses and programs, including Sackler, Fletcher, Medical, Dental, Nutrition, and the Gordon Institute. Mingle with old friends and new. We look forward to seeing you! Food and drinks will be served at this facilitated networking event.

TBBC Biotech BUZZ with Lily Ting: F Apr 14 — 9AM, M&V Lobby (Stearns 108)

Dr. Lily Ting is a life scientist and entrepreneur with 12 years of experience in academia and industry. Lily received her PhD from New South Wales University in Sydney and a post doc in the Gygi Lab at Harvard Medical School. After her experience leading projects in the academic sphere, Lily worked in a business development role at Athletigen and is now an Associate at PureTech Health. PureTech is a venture creation firm focused on bringing innovative solutions to the fields of neuroscience, immunology, and gastrointestinal diseases. She is also an avid dragon boat racer and just won gold, silver, and bronze in Puerto Rico!

TBBC Consulting Seminar Series: ClearView Heathcare Partners: Tu Apr 18 — 5-6:30PM, Sackler 507

Representatives from ClearView Healthcare Partners will speak to students about consulting and ClearView’s Connect to ClearView program for advanced degree candidates. 

TBBC, the Sackler Dean’s Office, GSC “Sackler Speaks” Flash Talk Competition: M Apr 24 — 5PM, Sackler 114

A well-developed flash talk is an effective tool to quickly and easily communicate your work to others. These take time to develop and usually evolve over a series of iterations. Sackler students will have a chance to give their scientific flash talks before a judging panel and other students. All presenters will receive helpful feedback and compete for nice prizes. This will be a low-key, fun event with appetizers and beer, and a chance to network with other students and professionals.

Recent Events

TBBC Biotech Buzz with Joel Batson, PhD, of RA Capital

F Feb 24: TBBC hosted Joel Batson, Science Project Manager at RA Capital. Joel introduced students to a new web-based tool he is developing and offered students the opportunity to collaborate with him and his team.

TBBC Career Seminar: Teresa Broering, Director of R&D, Affinivax

Tu Apr 4: Teresa Broering, current Director of R&D at Affinivax, a Cambridage, MA-based company developing a next generation approach in vaccine technologies, and former Director of Immunology at AbVitro as well as Senior Director of Product Discovery at MassBiologics, joined us for a discussion of her career path and her current role with Affinivax, and the current state of the biotech industry.

What Scientists Can Learn From Fiction Writers

Scientists don’t often think of themselves as writers. Our employment responsibilities do not include crafting characters or building worlds from words, nor investigating the latest political scandal, nor travelling the globe and composing reflections on our experiences. Yet, we do write: grants, reports, manuscripts. It is how we distribute our knowledge and the science we have done, because graphs and images and data have little impact if not shared. We write and revise as much as any journalist or novelist; still, writer isn’t an identity most scientists would primarily claim.

We are, though. Scientists are writers. Scientists are storytellers. Each graduate student, post-doc, faculty member has a story they are telling through their science. The scale and impact differs, but the fact remains: we must spin a tale convincing enough for our science to be funded, to be published, to matter. We are  writers, and we don’t even realize it.

I was trained to be a writer in the classical sense, specifically fiction writing. There were certain lessons that we learned over and over again, because they were fundamental to crafting even the most basic story. What fascinates me is that I have encountered these components informally in my graduate school training, just in the guise of doing good science.

We use basic story structure in writing articles: our beginnings ask a question, which we then try to answer in the middle, and our ends show how we have changed our little corner of the science world with our answer. There may even be a cliffhanger in there–alluding to a sequel coming soon to a journal near you!–if we’ve created even more questions with our answer. Grant writing uses a similar structure, with more emphasis on the cliffhanger. Leaving your reader on the edge of his seat, wondering what could come next, is something both scientists and fiction writers want (equally for the validation of having intrigued your audience and the satisfaction that such engagement often results in financial investment).

Show, don’t tell. Rather than telling a reader that a character is angry or sad, a writer should describe the character’s balled-up fists or tear-stained cheeks. For scientists, our equivalent of ‘telling’ is ‘data not shown’–and we all know how much we should avoid that. We do our showing in our figures. A scientist knows that the more data you can include, all the better. A scientist also knows that the more visually appealing your data is, the better it represents your conclusions. No one likes to read tables, right? Those data become so much more interesting as a pie chart, a graph, or a schematic. We show as much as we can, and tell as little as possible, because the best case scenario is when the data speaks for itself, instead of the scientist speaking for it.

Stories are much more interesting when they start in media res, or in the middle: no boring leadup, no extensive exposition. It is why publications often start with describing a hit or two they discovered from a screen, instead of the million little steps that led up to and happened during the screen itself. Good papers do that, and so does good fiction. The first Harry Potter book does not walk the reader through Harry’s childhood; it just starts right at the moment his life is about to change. Relevancy and immediacy are key components to telling any story, and scientists know and practice these principles to the best of their ability.

Crafting things out of thin air to make a story is a staple of fiction, but we know that as data fraud in the science world. The ‘characters’ in our scientific writing, the ‘plot’, the ‘setting’, the ‘rising action’, the ‘falling action’, all of those things have to be based on facts and evidence, on carefully planned and painstakingly executed experiments. They are based on reality. We know this; every scientist knows this. What we as scientists may not realize, however, is the extent to which fiction writing is also rooted in reality. Creating characters or worlds out of thin air is in actuality rarely done. The foundation of so many characters–ordinary or fantastical–come from experiences and observations within the writer’s own realm. It is a different way of collecting and representing evidence, a different way of asking or answering a question about the world. This reality-turned-fiction is one of the best ways a novel writer can build a sense of believability even in the most far-fetched fiction. It also builds trust between author and reader, one of the most important–and difficult–parts of fiction writing. Scientists have these components within their works as well, though constructed and strengthened in a different manner. Trust in science is built through executing proper and thorough controls, validating via different experimental methods, and considering (and hopefully, systematically eliminating) alternate theories or explanations. So regardless of the method in which they are built, that believability and that trust are critical components to any story, be it science or fiction.

Fiction writing, creative nonfiction writing, journalistic writing are all still very different beasts than scientific writing. Still, it would benefit scientists to focus less on the differences and more on where our often polarized fields actually do intersect. So much of our work is to provide convincing answers to difficult questions, and that type of evidence-based persuasion can be drastically more powerful if we use the same tools that traditional writers do. Scientists need to learn these tools as undergraduate and graduate students through formalized, structured, specified, and required coursework. That training will carry us, and our work, miles farther in graduate school and in our careers beyond. We need to be trained as writers, maybe as much as we are trained as scientists. Communicating our work in a persuasive and captivating manner is more important the ever, given the disturbing loss of faith in evidence-based arguments. We, as scientists, need to win that trust back, and to do so, we better be able to tell one hell of a story–to our funding institutions, to our public–about our science. For science to progress, we need our stories to be loud, to be spellbinding, to be believed and trusted by the public. We need to be writers, otherwise we might one day read a story about science that starts with once upon a time…

 

 

 

 

 

 

 

 

 

 

 

Opposites Attract: The Unlikely Marriage of Science & Fiction

Science, as a subject of study, often comes into conflict with other ways of thinking about the world. Religion. Philosophy. Art. The caricature of science as an opponent to these ‘humanitarian’ endeavors obscures the real relationship: symbiotic. In the case of science and literature, science provides fiction with an intriguing playground to muck around in, while fiction gives science a more human voice. This give-and-take between the two is what makes the genre of science fiction so rich, so enduring, and above all, so entertaining.

Science fiction more often than not uses science as a tool to explore other subject areas versus the science itself. It is not the engineering of the 20,000 Leagues submarine or the bioelectricity behind the monster in Frankenstein that makes these books long-standing members of high school reading lists. Readers are not likely spellbound by Margaret Atwood’s MaddAddam series mainly because of the intricacies of the genetic engineering catastrophe that ended her version of our world. No one likes Star Wars because of its explanations of the physics behind inter-galaxy travel. Fiction is not a mirror that reflects science to readers so that they can understand its most basic aspects. Instead, fiction is a prism that refracts science, fractioning and expanding it into its ripple effects and societal implications. It bends the bleached starkness of the discipline into a million different shades, spattering dark implications and bright hope for humanity in equal measure.

It is not always a fair coloring. Dystopia walks hand-in-hand with science fiction more times than not. Those stories do speak well of the perseverance of the human condition but often at the cost of vilifying some aspect of science. (Everything becomes a villain if left unchecked long enough, after all.) Still, fiction doesn’t just take from science; it gives as well. Science fiction is always ahead of its time, more audacious in imagining what human hands are capable of creating than what we believe is achievable at the time. With that creative inspiration, our history has shown it is inevitable that science fiction becomes science fact, from endeavours as incredible as space travel to tools as mundane as credit cards. And as such, science fiction has the privilege of not just asking can we, but also should we, and it has the added advantage of most times asking it first.

The audacious pushing of boundaries beyond the confines of the contemporary scientific knowledge within science fiction also creates a unique and rich environment for rebellion. Because in that type of story, in an imagined world that both is and is not this real one, what else could be different? Who else could become something more than what they are, or what society tells them they are?

This type of rebellion is what led to the existence of the genre itself. In 1666, the English duchess Margaret Cavendish published The Blazing World, a prose piece often considered one of the first utopian fictions and the precursor to ‘science fiction’ (a term not officially coined until 1926) as we know it today. Cavendish was an anomaly of her time, publishing plays, essays, and prose that tackled philosophy, rhetoric, and fiction, all under her own name instead of anonymously. She also was the first woman to attend a meeting of the Royal Society of London, despite fierce protest, and did not hold back in commenting on and even criticizing the scientific presentations and practices she observed. Her novel dove into discussions tackled by male authors of the time period–the conflict between imagination and reason or philosophy and fiction–but also was groundbreaking in two ways. First, she explored these topical areas within an alternate universe entirely of her own making but one that still used contemporary science of the era; second, her story strikingly centered on herself as the main character, where she traveled in between the two worlds. In a time where women were not considered capable of studying complex topics such as science, the Duchess of Newcastle used her writing to boldly carve herself a space in which she could defy that notion. In the process, she wrote into existence the first examples of many science fiction tropes still widely used today.

Her actions paved the way for other rebels, such as Mary Shelley, the mother of the first science fiction horror novel, Frankenstein. While a grey, depressing summer and a writing challenge born out of boredom provided an opportunity to craft her terror-filled story, her imagination was ultimately sparked after a firelit evening conversation with the controversial Lord Byron about what life is and how to create it. Despite being supported in her endeavours by her companions and her husband, Shelley ran into criticism upon publishing her work–incidentally most strongly from the specific publishers who knew the author was a woman–because it challenged the entrenched ideology of God being the only conceivable creator, not Man (or, in her case, Woman). In the deeply religious society of Victorian England, this was a revolutionary act.

Cavendish and Shelley may have been the some of the first authors to use sciene in fiction to challenge the social and moral status quo, but it was a tradition that persisted in the genre throughout the twentieth century. Starting in the 1960s, female authors were among the first to interrogate the definitions, implications, and biases associated with gender, class, and race. Ursula Le Guin’s sci-fi novel The Left Hand of Darkness–with its gender-fluid alien race dissecting what exactly gender and sex means outside of its Western civilization confines–led the charge. This breakthrough was followed by Joanna Russ’ 1975 matriarchal parallel-universes utopian novel The Female Man, then by Octavia Butler (who was the only African-American woman publishing in the genre at the time) and her late-1980s space trilogy Xenogenesis which explored race in addition to sexuality.

These revolutionary works also represent a broader theme within the genre: the influence of contemporary events of the era in which they were written. Science fiction is as much a reflection on the scientific knowledge of the day–and what could come of it–as it is on the historical and political backdrop of the time. Many early science fiction novels from the eighteenth and nineteenth centuries focus on stories of exploration and the technology that allows journeys into lands unknown. Most notable of these are Gulliver’s Travels (Jonathan Swift, 1726), 20,000 Leagues Under the Sea (Jules Verne, 1870), and The Time Machine (H.G. Wells, 1895). Historically, these centuries were flooded with exploration expeditions by European countries, and later the United States and Russia. While discovery for political and economic gain was the main purpose of most 18th century explorations, those carried out in the 19th century were more focused on deepening knowledge of the world, often through scientific observation and analysis. So, it is little wonder that the science fiction of the era reflected that desire to know more about the surrounding environments.

In the early 20th century, the domination of exploration themes in science fiction gave way to playing around in other subject matters–such as technology, biology, and medicine–which would later become genre staples. The early half of the century was one of rapid scientific advancement as much as it was political upheaval, and the collision of these two jarring phenomenons is reflected in the science fiction of the day. It was during this era that some of the seminal works of the genre were produced, including the post-Bolshevik revolution novel We (Yevgeny Zamyatin, 1924) and the science fiction classics Brave New World (Aldous Huxley, 1932) and 1984 (George Orwell, 1949). These novels each address how uncurbed scientific advances lead to a dystopian political society, and their thematic commonality clearly demonstrates the lasting impact several world wars and fast-paced science had on the public psyche of the time.

While dystopia strongly persisted within science fiction in the middle of the 20th century, the worlds crafted within genre novels did begin to grow a little less dire. As technological development continued to accelerate and started infiltrating daily life in the Western world–thus ‘normalizing’ it–likewise did the role of technology grow in fiction as androids and robots appeared on the genre scene. Authors of the time such as Isaac Asimov and Philip Dick couldn’t help but ask–and then answer through their writing–questions pertaining to the human condition in relation to the (imagined) creation and existence of non-human life. This philosophical bent echoed the early origins of the genre, going all the way back to Cavendish’s precursor work, demonstrating how far the genre had progressed.

Glancing back and paying homage is all well and good, but science fiction also found new ways to move forward at the end of the 20th century. In 1979, The Hitchhiker’s Guide to the Galaxy added a little laughter and good humor to the genre, breaking ground for many others to follow across even until today. The gloom of the war-torn early decades also seemed to have worn off, with a revitalization of the previously ‘tired’ utopian sci-fi tradition by Kim Stanley’s Mars trilogy in the 1990s. This trend of revitalizing and redefining the genre has persisted into recent years, with the semantic alteration by Margaret Atwood, who calls her novels not ‘science’ fiction, but speculative fiction. In her MaddAddam series, she reaches for what might be just possible in the realm of science and society, instead of the complete impossible. In some ways, this approach brings about an even more imaginative (and frightening, and wonderful) vision of what the human mind can create when challenged in the perfectly right and wrong ways.

Ultimately, the fiction of science is as elusive and ever-changing as the real thing. It circles itself: thought and action, can and should, might and will and have done. Whether we as scientists today use science fiction as inspiration–or as a warning–only time will tell.

GSC Committee & Club Updates: December 2016

Tufts Biomedical Business Club (TBBC)

from Aaron BernsteinCMP

Upcoming Events

TBBC Case Study Group: Mondays – 5-7PM beginning M Feb 6, Jaharis 508

Practice solving cases, gain insight and tips, and learn more about the field of consulting.

Recent Events

TBBC Seminar Series: Liz O’Day, Founder and CEO of Olaris Therapeutics

Tu Dec 6: Liz O’Day, PhD, presented actionable tips and insight into her transition from the academic world to being an entrepreneur. Olaris is a venture-backed drug discovery company that uses a proprietary NMR-metabolite profiling platform to unlock aspects of human metabolism that could never before be analyzed.

TBBC Consulting Seminar Series: Peter Bak, PhD

Tu Dec 13: Peter Bak, PhD, Manager at Back Bay Life Science Advisors, spoke about transitioning from a PhD program to life sciences consulting and career opportunities at BBLSA.