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Coffee & Conversation with Dr. Laverne Melón

Written by Alyssa DeLeoNEURCoffee & Conversation is a series of informal chats with women faculty on campus, hosted by Tufts GWiSE. 

Our last Coffee & Conversation of the year featured Dr. Laverne Melón, a post-doctoral fellow in the Maguire lab and a TEACRS scholar. She will joining Wesleyan University as a faculty professor in neuroscience in the Fall. Laverne was born in Trinidad and moved to New York when she was 10 years old. In high school, Laverne helped establish the science club, which she insists was the most poppin’ after school extracurricular at the time, and she knew she wanted to work in research before even knowing what that was. The science club gave her and her peers the chance to support each other in the search for research experiences and ultimately lead her to volunteer in a cancer genetics lab at Columbia University. As she reflects on her first experience in science, she also acknowledges that it was also her first exposure to the sexism and racism that exists in scientific institutions. It’s difficult to turn a blind eye to these situations when all you want to do is put your head down and do the work in front of you. But, she didn’t let this taint her passion for the field and her experiences spoke to her resilience, which would be noted by several scientists later in her career.

Laverne went on to earn a BA in neuroscience at Middlebury College, a MS in Behavioral Neuroscience at Binghamton, and a PhD in Addiction Neuroscience at IUPUI after her lab at Binghamton moved. She lost a Binghamton fellowship in the move and had to teach at IUPUI, which she found frustrating as anyone does when they’re forced to do something. However, Laverne began to enjoy the process and her career path in academia became increasing clear. Laverne has been a post-doc in Jamie Maguire’s lab for the last 4 ½ years studying effects of stress on reproductive health and the role of the GABAergic system in alcohol addiction. As she moved into her post-doctoral years, she was really fueled by a research question which she presented to Jamie along with some data to score her current position. Now, she’s fielding multiple offers for faculty positions and learning to navigate this new part of her career.

As always, we chatted about how early life experiences brought our guests to their current positions, how crucial the role of mentors played in this trajectory, and the vital importance of self-advocacy. But, we kept coming back to this idea of producing good, reproducible science and how that is only possible if the field really cared about the people behind the data. It’s no secret that scientific institutions have not been the best advocates for the health of their workforce. Levecque et al. published a study in May of 2017 reporting one in two PhD students experience psychological distress and 1/3 of graduate students are at risk for a psychiatric disorder. An online survey of graduate students in a recent March 2018 study by Evans et al. reports graduate students are more than six times as likely to experience depression and anxiety compared to the general population. SIX times! It’s exceeding clear that health of scientists across fields and levels are struggling in this environment. This begins by hiring scientists that are more than a good researcher, but are inspired teachers, passionate mentors, and expert managers who are in touch the health of their lab.

As Laverne is beginning the next chapter of her career, she’s considering taking on an administrative position as a director of inclusion and diversity in addition to her faculty appointment. She intends to use her status to implement institutional changes to allow for better science through caring, supporting, and mentoring the next generation of scientists. When Laverne started to work in science, she admitted she tried to assimilate as much as possible, but it gets exhausting. It’s difficult to integrate into establishments and systems that have been hostile to the existence of women and minorities in science while trying to stick it out until you can get to a position to make changes. She’s been able to tap into her mentoring network over the years for support and instructed us to be vulnerable in our insecurities to allow these organic mentorships to grow.

If you’re interested in getting involved with GWiSE, follow us on Twitter @TuftsGWiSE, like us on Facebook, or email us at tuftsbostongwise@tufts.edu. Our next Coffee & Conversation is October 19th, 2018 at 5PM in Jaharis 913.

Green Labs: How to be environmentally sustainable in biomedical research

The main responsibility of a biomedical researcher is to produce novel, trustworthy science that will improve human health. We may not be doing enough towards this goal, however, if we consider our research results to be our only impact on the human condition. How we conduct our research is just as critical as the results of our research, especially when it comes to the environmental footprint that research laboratories leave behind on university and medical campuses.

In 2013, Tufts University published a campus-wide report to assist the university in building a sustainable future. Working groups focused on three relevant sustainability areas—energy and water use, waste management, and greenhouse gas emissions—to develop actionable goals for reducing Tufts’ environmental impact. Regarding how laboratories and medical facilities factored into this impact, all working groups came to the same conclusion: “[these spaces were] singled out…as the greatest source of opportunity for increased sustainability across all Tufts campuses due to their large production of waste and heavy use of water and energy.”

Tufts is not the only university facing these issues. Harvard University labs consist of  20% of physical campus space but account for 44% of their energy use, and MIT labs take up less than a quarter of campus space but account for up to two-thirds of their energy use. So, if scientists like to talk the talk when it comes to best practices in advocating for governmental and community support of sustainable practices, how can we commit to similar support within our own institutions?

Many universities, including Tufts, have implemented Green Labs initiatives in order to develop environmentally friendly research laboratories using a classic sustainability framework: reduce, reuse, recycle. Based on resources from Tufts’ Green Labs Initiative and similar programs at other institutions, here are some starting points for making laboratories and research facilities more sustainable.


REDUCE

Energy: Labs can significantly reduce energy usage by maximizing the efficiency of their ultra-low temperature (ULT, or -80°C) freezers, as in one year, a single ULT freezer uses the same amount of energy as an average American household. Frequent de-icing, regular upkeep, and maintained organization all decrease the amount of work and time (and thus energy) required by freezers to decrease temperature to the set point. To encourage these approaches, Tufts joined the International Freezer Challenge in 2017, which rewards best practices in cold storage management”. Of note, three Sackler labs–the Munger lab, the McGuire lab, and the Bierderer lab–participated. Additionally, a less universally advertised, but possibly more effective, approach to reducing energy usage by ULT freezers is changing their set temperature. The University of Colorado at Boulder has accumulated a significant amount of information demonstrating that maintaining ULT freezers at -80°C may not be necessary, as many sample types are capable of being stored at -70°C without any significant loss of quality. Though seemingly trivial, this ten degree difference has huge implications for lowering energy usage , which also translates to reduced energy costs (Figure 1). By rough estimation, Tufts could save close to $50,000 per year on electricity if all ULT freezers in Jaharis, M&V, Stearns, South Cove, and Arnold were adjusted from -80°C to -70°C.

†Number of ULT freezers was calculated by presuming 5 freezers per floor in Jaharis 6-9 and 10 freezers per floor in Jaharis 3-5. This estimate was extended to the remaining buildings on the Sackler campus.

Figure 1. Yearly energy expenditure & cost savings for ten-degree increase in ULT freezer temperature.

Closing and/or turning off chemical fume hoods when not in use also mitigates electrical expenditure. At the Medford campus, undergraduate student Emma Cusack led a “Shut the Sash” initiative last year in order to reduce energy use and cost. Based on consultations with the Tufts’ Office of Sustainability about her work, it is estimated that lowering sashes of all 123 chemical hoods on the Sackler campus from 18” to 6” when not in use would result in yearly energy expediture savings of around 40,000 kWh and energy cost savings of over $200,000.


Figure 2. Yearly energy expenditure & cost savings for reducing sash height of chemical hoods. 

Lastly, powering down non-essential lab equipment overnight and incorporating timers into power sources are also simple but meaningful methods of lowering energy usage. The latter method is especially helpful to maintain convenience along with energy efficiency, as incubators and dry ovens are shut off overnight but can still be ready-to-use upon arriving in lab, for example, if set to turn on in very early AM.

Water: A traditional autoclave requires 45-50 gallons of water per minute when in use, and this massive usage is due to the need for continuous addition of water for cooling steam condensate before draining into sewers. Equipment like Water-Mizers use real-time monitoring of drain temperature to add water for cooling only when needed, reducing water usage by at least half. Also, being mindful of when sterilization is actually required for equipment and using dishwashing services as an alternative also contributes to lowering water usage.

Within labs, addition of low-flow aerators to faucets and switching vacuum sources for aspirators from faucet-style to vacuum-style can also can significantly reduce water usage. Finally, being conscious of when it is really necessary to use distilled or deionized water, as the process wastes water that does not pass the filtering thresholds, can also contribute to making water usage by labs more efficient.


REUSE

Materials: Styrofoam shipping containers and freezers packs can accumulate quickly in labs, given the frequency at which supplies are ordered and received. However, they are not necessarily easy to get rid of in sustainable ways. Many labs end up reusing some fraction of the styrofoam boxes and freezer packs they receive for experiments, which seems to be the most common and easily practiced alternative to throwing these shipping components away.


RECYCLE

Materials: Another approach for sustainable disposal of styrofoam and freezer packs is recycling them. A handful of life sciences companies do sponsor recycling programs for styrofoam containers, including Sigma-Aldrich, Qiagen, and New England BioLabs (which has run such a program for over thirty years), but most companies do not, given the cost of such programs. Alternatively, for-hire companies specializing in styrofoam recycling can be contracted by universities, but again the associated cost can be a deterrent. Even rarer are return programs for freezer packs, as the combination of contamination concerns and the cost of re-sterilizing seems to discourage their implementation.

The amount of plastic materials that biomedical research labs use are also quite high, though recycling used materials such as pipette tips, serological pipettes, conical tubes, or microcentrifuge tubes is often not convenient or feasible due to biological contamination. However, containers for materials (i.e. cell culture media bottles, pipette tip boxes) can be sterilized and disposed of much more easily. In the case of pipette tip boxes, several companies–such as Fisher Scientific, USA Scientific, Corning, and VWR–do sponsor programs where discarded boxes are collected or received via mail for recycling.


While achieving greener laboratories first requires implementation of sustainable practices like those listed above, the success of such efforts ultimately depends on institutional support and researcher engagement. Even if such resources and programs are offered by companies or research institutions, scientists need to be made clearly aware of their existence to take advantage of them. Accordingly, university- or departmental-level promotion of and encouragement for sustainable practices could substantially increase researcher interest and participation. Implementing reward-based systems, including financial incentives, for labs that ‘go green’ could also help motivate investigators to commit to practicing sustainable science.

In being more conscious of the environmental footprint that biomedical research leaves behind, scientists can clean up our own backyard and stand on firmer ground when encouraging others to do the same.


Thank you to Tina Woolston and Shoshana Blank from the Tufts Office of Sustainability and to Stephen Larson and Josh Foster from Tufts Environmental Health & Safety for providing information and resources on chemical hood numbers, energy usage, and costs.


Resources

Tufts University: http://sustainability.tufts.edu/get-involved/tufts-green-labs-initiative/

http://sites.tufts.edu/tuftsgetsgreen/2017/07/28/the-green-labs-initiative-an-overview/

University of Colorado: https://www.colorado.edu/ecenter/greenlabs

EPA Greenhouse Gas Equivalencies Calculator: https://www.epa.gov/energy/greenhouse-gas-equivalencies-calculator

Laboratory Fume Hood Calculator: http://fumehoodcalculator.lbl.gov/index.php

 

 

Career development initiatives, curriculum design, & building networks discussed at Sackler Community Meeting

This past June, around seventy-five graduate students and faculty members joined Dean Dan Jay and Associate Dean Dan Volchok in the DeBlois Auditorium to reflect on the previous year’s progress and endeavors at the Sacker School. Various community leaders briefly presented on topics that reflect the Deans’ new mission of training to career excellence followed by open discussion between all attendees. Following the larger meeting, attendees continued to engage in these topics in smaller groups over lunch to continue pushing these goals forward in the coming year.

Jay opened the meeting by reviewing the results of career development “trial balloons” that the new administration worked towards last year. He celebrated the high interest and positive reactions from trainees for the new short courses, including Introduction to Drug Development (50 attendees), Navigating the Corporate Environment (22 attendees), and the R Programming Workshop (34 attendees). Building on this positive momentum, additional short courses will be offered in the coming year. A ‘science storytelling’ workshop and an entrepreneurship short course have been developed for the fall semester, with a teaching short course planned for the spring. There are also plans to develop the Introduction to Drug Development course into an official Sackler-wide elective for the spring semester. In addition, two career counseling workshops by Sarah Cardozo Duncan will again be offered in the 2018-2019 for students and post-docs who are interested in industry-related careers.

Not all career development endeavours in Sackler last year had such immediate success, however. The initiative to place students who have completed Year 1, Year 2, or their thesis requirements in summer industry internships encountered several difficulties, including reluctance from potential partner companies. That reluctance mainly stemmed from aversion to such a short internship time period (3 months), as several companies in conversation with Sackler administration requested at least a 6-month full-time commitment from students. Meeting attendees generally agreed that this length of time would be difficult for both PIs and students to commit to without serious disruption to research progress. However, there was at least one successful internship negotiation and placement, suggesting that the program may still be developed but not in as broad a manner as originally intended. A case-by-case determination was concluded to be the best approach moving forward, with the requirement for extensive conversations and mutual agreement between student, PI, and hosting company on timeline and degree of commitment being emphasized.

In reiterating his desire to see Sackler become a leader in career training for biomedical graduate students, Jay described his aspiration to develop a tuition-bearing, two-year master’s program in Biomedical Leadership. Matriculating students would have the opportunity to train for various career tracks related to biomedical research, and their curriculum would include current and future career development short courses or electives offered within Sackler. During the group-wide discussion session, the possibility of offering a 4+1-style master’s program in collaboration with the undergraduate branch of Tufts University was put forward and positively received.

Another main topic of the community meeting was the state of graduate research training at Sackler. Opening discussions involved debating the merits of switching from the current program-specific curriculum design to a single core curriculum that all first-year graduate trainees–regardless of program–would take. Across programs, students generally were opposed to a core curriculum in regards to scientific content, emphasizing that most seek a graduate education specifically to specialize in a particular area. They did support the suggestion that any core courses in scientific content should be ‘nanocourses’, instead of full required or elective courses. In contrast, developing a skills-focused core curriculum that included classes such as research methods, quantitative biology & bioinformatics, and statistics seemed to have wide support from both students and faculty.  In addition to curriculum content, the possibility of expanding the MERGE (Medically-Oriented Research in Graduate Education) beyond the Immunology and Molecular Microbiology programs was discussed. The MERGE program trains participants in clinical aspects of their research area during the summer prior to their first graduate year at Sackler. During this time, they are also paired with a clinical mentor who provides them direct contact with patients and clinicians and serves as a thesis committee member during their research training. Given the proximity of Tufts Medical Center, it was advocated for the Sackler School to take advantage of the opportunity to give more PhD students training in regards to the clinical impact of their research. Genetics and Neuroscience were considered as programs which MERGE could expand to, but no specific plans for that expansion were discussed.

Strengthening the Sackler community was also a significant theme of the meeting. During a discussion about building diversity and inclusion at Sackler, students expressed the need for more structured support from the school. They expressed that while student-led initiatives such as SPINES (Students Promoting Inclusive Excellence at Sackler) provide excellent resources and opportunities for underrepresented minority (URM) students, the responsibility of delivering such support should not fall so heavily on the trainees themselves. Through this discussion, it was emphasized that bringing more URM junior faculty–from Tufts or other institutions–to speak at graduate seminars could help build networks for students to rely on. In addition, hosting a greater number of Sackler-wide events during the year, especially during recruitment, could foster a greater sense of community and provide more school-directed opportunities for URM individuals to connect across programs. Another discussion about community building focused on developing stronger alumni networks. The career development short courses were one way in which the Dean’s Office started on this initiative already. Various alumni contributed their expertise and their time to the courses’ development and operation, which was key to their success; this arrangement also provided a structured environment in which students could take the opportunity to develop professional connections with alumni in their career areas of interest. Given the positive outcomes from this year using this approach, there are plans to build on this foundation for similar endeavours in the future. Dean Jay also discussed his efforts over the last year in reaching out to Sackler alumni for fundraising, which he had done in collaboration with Roxanne Beal from the School of Medicine’s Office of Advancement and Alumni Relations. To broaden this effort, faculty were encouraged to reach out to their former trainees, and the group supported the idea of current students reaching out to alumni for an annual fund.

Overall, the morning and lunchtime discussions provided great insight into the past year’s success as well as highlighted what aspects of graduate training at Sackler still need to be strengthened, and the dialogue between students, faculty, and staff generated actionable items for the administration to take on in the coming academic year.

Novelty is in the eye of the beholder: The process of writing an F award application

The image used here is released under Creative Commons CC0.

Writing an F award application is kind of like a jigsaw puzzle. There are lots of pieces, they all need to fit together just so, and it feels like it will never be complete. But writing – whether it be manuscripts, reports, or grant proposals – is a huge part of any scientist’s career, and it shouldn’t be an unpleasant process. F awards, which provide a stipend, health fees, tuition, and travel, are a great first step into the world of scientific writing.

There are a few oft-repeated adages that are thrown around when it comes to grant proposals, such as “Make your aims related, but independent” and “You need to study a little bit of a mechanism.”  While these are helpful in their own way, here are some other tips to make applying for your first F award a bit smoother:

  1. Take advantage of info sessions

Sackler offers two information sessions every year for potential F30 (M.D./Ph.D.) and F31 (Ph.D.) applicants. If you have questions about when to apply, writing, or anything else, this is the place to ask them. An additional day-long workshop is being held for the first time this year, hosted by Dean Dan Jay.

The Application – June 5th, 2 – 3:30 PM

Demystifying the Review Process – June 7th, 2 – 3:30 PM

*Writing Your Specific Aims – June 15th

*Attendance at the first two session is required for this workshop. Attendance will be limited to 20 participants.

  1. Make a list

There are several pieces to this application – so many that it’s possible for some of them to fall through the cracks. A checklist is a simple way to ensure you won’t need to rush to complete a document (or worse, start writing it!) minutes before the deadline. The following list is accurate as of Spring 2018:

  • Abstract/Project SummaryApplicant’s Background and Goals for Fellowship Training
  • Bibliography and References Cited
  • BioSketch
  • Cover Letter
  • Equipment
  • Facilities and Other Resources
  • Institutional Commitment
  • Letters of Support
  • Project Narrative
  • Research Strategy
  • Resource Sharing Plan
  • Respective Contributions
  • Responsible Conduct of Research
  • Selection of Sponsor and Institution
  • Specific Aims
  • Sponsor Information
  • Sponsor’s BioSketch
  • Vertebrate Animals

If you’re resubmitting your application, you’ll also need to include an “Introduction,” a one-page document where you respond to the criticisms of each reviewer.

  1. Gather preliminary data

To the bench! With data in hand, you can work with your advisor to determine what kind of story you want to tell. Your goal here will be to gather data that will demonstrate the feasibility of your proposal. Starting early is key, as this process can take several months. The more data you have, the better. It shows the reviewers that you can work hard and be productive.

  1. A picture is worth a thousand words

Begin crafting your figures before writing. Figures are a visual representation of your story; having it effectively “storyboarded” out makes it easy to see where there are holes in your data. Patching these now makes for a much stronger initial application.

  1. Make your Aims into an outline

Your Specific Aims page functions as an overall summary of your proposal. While your reviewers must read the whole proposal, you should assume that most other panel members will only scan this section. All of the critical aspects of your proposal should be clearly stated here, including the impact and novelty of your research.

  1. Stagger writing with editing

Once you write your initial aims, send it to your advisor for comments and get started on the next piece of your application. As your advisor returns documents with comments, you can edit and send them back. A continuous cycle of writing, editing, and rewriting keeps the process moving and keeps you from working on the same document for too long. You’re more likely to catch typos and other errors by looking every so often with fresh eyes.

  1. Play the matching game

Consistency is huge in any F award application. You will reference your aims multiple times in the Research Strategy section. As you craft your proposal, make sure that the methods listed under each aim match in the Research Strategy and Specific Aims sections.

  1. Ctrl-F for key words

There are certain core concepts that, when missing, are easy for reviewers to point out as a flaw. Your application should not only comment on the novelty and innovation of your proposed research, but also include key phrases such as “sex as a biological variable.” Reviewers may simply search for these terms to see if you address them, so you should do it, too. Talk to your advisor for some examples. As someone who writes and reviews grants, they will know exactly what they would look for in a proposal.

  1. Skip the jargon

Not every reviewer you have will be an expert in your field. In fact, it’s likely that none of them will be familiar with your precise topic of interest. If a simple word will do the job, use the simple word. The less reviewers have to think about what you’re trying to say, the better they will feel about your proposal.

 

Easier said than done, right? Don’t be discouraged if your proposal isn’t funded in its initial submission. Only about 13% of applications are at Sackler. However, making the strongest proposal you can initially will make it easier to edit for resubmission, and much more likely to be funded the second time around. Over the last five years, Sackler applicants have had a 30% success rate (this number includes both proposals funded initially and those funded after resubmission). For a breakdown of success rates by NIH institute, check out the following link: https://report.nih.gov/success_rates/. The F30/F31 spreadsheet is #3 under “Training and Research Career Development Programs.”

Finally, take a break once you’ve submitted the proposal! Rest and recharge before returning to the bench so you can get ahead on your next project.

 

Sources and Related Reading:

  1. NIH. Write Your Application. Last updated: 2016 Jan 28 [cited 2018 May 17]. Available from: https://grants.nih.gov/grants/how-to-apply-application-guide/format-and-write/write-your-application.htm
  1. Chasan-Taber L. 10 Tips for Successful Grant Writing. The Chronicle of Higher Education. 2018 Feb [cited 2018 May 17]. Available from: https://www.chronicle.com/article/10-Tips-for-Successful-Grant/242535
  1. McCollum, L. To Resubmit or Not To Resubmit? GradHacker. 2015 Feb [cited 2018 May 17]. Available from: https://www.insidehighered.com/blogs/gradhacker/resubmit-or-not-resubmit
  1. Hollenbach, AD. A Practical Guide to Writing a Ruth L. Kirschstein NRSA Grant. 1st ed. Oxford: Academic Press; 2014.

• This resource is available from Hirsh Health Sciences Library.

Relays Are Coming – Graduate Student Council Holds Open Meeting

The Sackler Graduate Student Council (GSC) held an open meeting last week, on April 5, 2018. The turnout was good – every program had at least one non-GSC student at the meeting. “We want people to know what we do,” Rebecca Silver, our current GSC President, stated.

GSC meetings generally begin with an update from the treasurer, a monthly recap from the three sub-committees (Career Paths, Social, and Outreach), and conclude with action items. As the environment was low-key, non-GSC attendees comfortably offered thoughts and ideas on a variety of matters. If you want the low-down on what events the sub-committees have planned, check out The Goods email (arriving in your inbox weekly).

Sackler Relays was a big topic at this particular meeting. The event has been set for June 8th (mark your calendar!) and subjects ranging from raffle prizes to activities to food were discussed. A popular idea was to potentially have a faculty team for the first time – who doesn’t like a little friendly competition? All in all, a productive meeting. “And at the end of the day,” Silver said, “everyone got some free pizza!”

Chatting with the non-GSC attendees after the event, it was clear that many were curious about the kind of delegation that occurs on the council, wanted to have input, or were interested in becoming a representative for their program in the future. Just remember, according to the bylaws, all GSC meetings are open, and you can get in touch with your program rep(s) if you’re interested in attending regularly. GSC wants to hear your ideas!

Relays Are Coming

Book Review: The Scientist’s Guide to Writing

It’s not uncommon to hear young, aspiring scientists say, “I hate writing. That’s why I’m going into science!” Plot twist: we do a lot of writing as scientists. Writing is pervasive in this field. We write to disseminate our research to the wider scientific community, to get funding, to get hired. It’s surprising that, as a community, we don’t devote much time to formally training students in the writing process.

Enter Stephen Heard, an evolutionary ecologist, who wrote “The Scientist’s Guide to Writing” to help address this gap in training. He draws from the scientific study of scientific writing, filling in the gaps with his own experiences with the writing process. The result is a book that not only advises readers on what to include in different written works, but also provides exercises that can be used to improve their use of the craft.

When scientists write about their research, the goal is mainly to convince other scientists that the body of work is important, and completely necessary, to the advancement of a particular scientific field. To do this, any arguments made need to be clear and well-founded, easily transferable from the page to the reader’s brain. Heard addresses this by offering his reader details about what writing actually is, beginning with the history of scientific writing and its unique evolution.

Throughout the book, Heard draws his reader to several conclusions, including three crucial tips: first, that any body of work must be crystal clear (in his words, it should “seem telepathic”); second that making note of things you like when you are reading can bolster your own writing; and third, that every word should be considered and removed if unnecessary. These conclusions apply across the board—not just to manuscripts, but also to grants and other types of scientific communication.

While a book on writing may not seem especially interesting, Heard’s advice is invaluable to the developing writer. Reading this, or a similar book, should be considered critical training for every student of the sciences.

Sci-Art Contest 2017: And the winner is…

Last month the Sackler Insight hosted a contest to find the best science-based art (“sci-art”) at Sackler. All twelve entries were posted to the Sackler Graduate Student Council Instagram account (@SacklerGSC) and the Sackler student Facebook group. The winning contributor will receive a $25 Visa gift card!

The results are in! 174 voters from both Instagram and Facebook weighed in on their favorite pictures. Our lucky first place winner is Mary H. from Microbiology with her photo “An enteroid supernova,” which received 65 votes. Runners-up included Rana A. from PDD with “Making the best of a bad Western” (61 votes) and Rob C. from CMDB with “Monday Blues – Screening One-Bead-One-Compound Peptide Libraries” (39 votes).

Congratulations Mary, and thank you to everyone who participated! You can check out the pictures below:

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.”

Greentown Labs is at the Forefront Boston’s Cleantech Industry

In the wake of hurricanes Harvey and Irma, I feel compelled to understand what cleantech strategies are currently available to tackle climate change. California’s cleantech industry was an obvious thought that came to mind. Over the past decade, California’s institutions and companies have been leaders in the U.S. market for producing clean energy and biodegradable materials. This past summer, the Joint BioEnergy Institute (JBEI) in the Bay Area received federal funding for innovation in biofuels and bioproducts. Since its inception, JBEI has yielded several startups that are committed to engineering microbes and crops to convert sugars into high-value renewable fuels. But where does Massachusetts stand in the cleantech industry? Fortunately, we’re not too far behind.

The nation’s largest cleantech startup incubator actually exists right here in Massachusetts. The Somerville incubator Greentown Labs hosts more than 100 startup companies and has raised over $200 million in investor funding since its founding. There is an emphasis on solar, wind, and wastewater technology in this incubator that is very unique. For example, the startup WrightGrid has developed a single solar-panel-based charger for robust cell phone charging in rural areas. Furthermore, SolChroma has developed full-color reflective digital billboards that reduce light pollution and energy costs in big cities. The company Sistine Solar can come to your home and design personalized solar panels in all aesthetic shapes and colors, enticing homeowners to switch to solar energy. One company that piqued my interest was Spyce, a startup intersecting food and technology. The company has developed a robotic kitchen that can serve meals with fresh ingredients in less than five minutes. The robotic kitchen is compact and reduces the amount of space and manpower that is typically needed at restaurants to prepare meals.

For the global market, Greentown Labs hosts Promethean Power Systems, a company that manufacturers rural refrigeration systems in off-grid and partially electrified areas of developing countries. In the same vein, Ivys Energy Solutions provides renewable hydrogen fuel cells to the international market. For the agrigulture sector, Raptor Maps fuses drone-based imaging technology to detect pest and weed infestation so to reduce water usage and nutrient management. Multisensor Scientific has also developed imaging capabilities to visualize and quantify in real-time methane leaks from natural gas infrastructures, thus reducing harmful methane emissions that are driving climate change. In the materials sector, Alkemy Environmental recycles industrial waste into lightweight concrete. For water management, Aquafresco is reinventing how we do laundry through a wastewater recycling invention that reduces the amount of water we use by 95%

Just a week ago, Tufts University collaborated with Greentown Labs to support cleantech solutions. The agreement between the parties will allow them to share their expertise, resources, and networks. The collaboration is also exciting because it allows for startups run by Tufts affiliates to directly become members of Greentown Labs. Currently Greentown Labs is tight on space but they are opening up a new building in Somerville next month to host more startups. The expansion of Greentown Labs is very promising for the future of cleantech in the Boston area. Just like Kendall is synonymous with biotech, in the next few years Somerville will be synonymous with yuppies, hipsters, and, perhaps, cleantech.

References:

http://www.xconomy.com/san-diego/2017/06/19/synthetic-genomics-breakthrough-algae-produces-twice-as-much-oil/#

 

https://now.tufts.edu/news-releases/tufts-university-collaborates-somervilles-greentown-labs-support-inventive-clean

 

https://www.wheretraveler.com/boston/eat/boston-food-tech-future-just-got-delicious

 

https://www.greentownlabs.com/about/

 

http://newscenter.lbl.gov/2017/07/17/doe-renews-jbei-funding/