ICYMI: Short course on Introduction to Drug Development

The fall semester is in full swing here at Tufts, and Dean Dan Jay’s mission to “train to career excellence” is already palpable. You may have noticed that you received an e-mail alerting you to new course offerings at Tufts this fall: a career coaching workshop that also includes one-on-one sessions with career strategist Sarah Cardozo Duncan (this took place on October 16, 2017) as well as a short, five-week course on drug development, led by Tufts alumnus and Agios Pharmaceuticals’ director of enzymology Stefan Gross, PhD.

As a “senior grad student” (don’t call me that to my face), the impending decisions of career paths are pressing on me. Since I had met Stefan at other Sackler events–he gave a DMCB seminar as well as judged our flash talk competition last spring–I knew he was a fantastic scientist and speaker. I jumped at the opportunity to learn from him first hand about the work he is involved in, and registered for his course on drug development. In this edition of “In Case You Missed It,” I’ll be sharing with you my experience at our first class. Perhaps it will inspire you to also take other career training courses that we anticipate will be offered in the coming semesters!

In this first class, Stefan talked about developing drugs for strategically selected diseases- for example, rare genetic diseases that are relatively uncommon but are actually prevalent enough for a substantial patient population (and ultimately drug consumer population) to exist. We reviewed a specific example that covered the series of experimental techniques performed toward developing treatments for an example of a category of rare genetic diseases, Congenital Disorders of Glycosylation (CDG). As the name CDG suggests, these conditions are due to defective glycosylation, the ubiquitously important process in which a carbohydrate is attached to a molecule to enable its structural or functional role. Glycosylation defects can occur at many different points of sugar production, and for every affected step in the pathway, there can be an associated disease. We learned about how to design an experiment to screen thousands of compounds that might rescue enzymatic activity of phosphomannomutase 2 (PMM2), a defective enzyme in a type of CDG. Moving forward, we also learned how to follow up on and validate hits from a screen and then progress those compounds through a drug development program.

Just from this first meeting, I can tell this course is unlike any other I have taken at Tufts (and as a one-time Immunology, now-CMDB student, trust me, I have taken many). The mix of graduate students and postdocs, as well as the presence of our Deans Dan and Dan, creates a new kind of diversity and range of experience that results in many thought provoking questions, comments, and discussions. I look forward to completing the class goals outlined by Stefan, which are to familiarize ourselves with the small molecule drug discovery process and current state-of-the-art concepts in drug discovery, and to conduct a company diligence exercise. Towards the first two goals, we will be learning about procedures carried out at industrial companies that often require resources graduate students like ourselves could only dream of, like simultaneously testing thousands of 96-well plates with tens of thousands of compounds in a screen. By thinking about science through a lens in which we are enabled with benefits like these, experiments can be designed in a completely different way. Furthermore, the third goal of the course, to conduct a company diligence exercise, is meant to prepare us for an interview at a biotech company, something that your microbial genetics course may not.

Keep an eye out for announcements for career-oriented course offerings in the future. These are great opportunities for those of us who may be interested in transitioning to a career in industry after grad school, and even for those who have other paths in mind but are still curious about the inner workings of industrial procedures!

On the Shelf…

SpringerNature Experiments

For Work

Springer Nature Experiments

Location: Coming mid-October, look for announcement on HHSL website

Springer Nature Experiments is a new platform that searches four protocol and method resources simultaneously: Springer Protocols, Nature Protocols, Nature Methods, and Protocol Exchange, providing easy access to more than 50,000 protocols and methods.

Unique indexing means that you can quickly find protocols and methods for a particular organism, common and emerging techniques, or videos.

The summary page for each protocol and method provides an abstract, version history, figures and videos from the article, and the number of citations the article has received.  This information helps you choose the best protocol or method for your work without scanning multiple articles on different sites.  When you find one that works, then you can click through to the full text, available through Tufts Libraries.


 Patient H.M.: A Story of Memory, Madness, and Family Secrets

For Leisure

Patient H.M.: A Story of Memory, Madness, and Family Secrets, by Luke Dittrich

Location: HHSL Book Stacks WM 173.7 D617 2016

The story of Henry Molaison, who lost his ability to create memories after a lobotomy, the man who performed the surgery (the author’s grandfather), and psychologist who studied Mr. Molaison for decades.

PubMed Tip of the Month…PubMed vs. PubMed Central

I often see people confuse PubMed and PubMed Central.  While these two resources are linked to one another, they are separate and distinct.  Here is a summary of the two:



PubMed Central (PMC)

What is it? Citation & abstract database Full text repository
What am I searching? ·        Citations to journals indexed for MEDLINE, including out-of-scope articles (e.g. Nature article on plate tectonics) and articles not yet indexed for MEDLINE

·        Citations to articles in PubMed Central

·        Citations to books available on NCBI Bookshelf

·        Articles/manuscripts deposited by publishers or authors to comply with funder public access policies

·        Complete issues of journals that choose to deposit their full contents in PMC


How should I access & use? ·        Freely available

·        For links to full text articles through Tufts Libraries, access PubMed via the Hirsh Health Sciences Library website (‘PubMed @ Tufts’ from Databases tab, or under Quick Links)

·        While at Tufts (or any other institution that purchases journal subscriptions), do not use the ‘Free full text’ filter on a PubMed results page because this limits results to only those articles that are freely available to the public

·        Freely available

·        Can access directly, but usually no reason to do so

·        Look for ‘Free PMC Article’ link below article in PubMed list of results, or PMC button in PubMed abstract view

·        NIH Public Access Policy: all peer-reviewed journal articles that arise from NIH grant or cooperative agreement must be deposited in PMC & made publicly available no later than 12 months after publication


Top Techniques: So you want to study metabolism…

Written by Daniel Fritz and Judi Hollander


When studying the phenotype of a particular cell line or observing changes after cell treatment it is often desirable to establish the relative contributions of various metabolic pathways.  Agilent’s (formerly Seahorse Bioscience’s) Seahorse XF Analyzer fulfills the role of a capable, easy-to-use platform to gather important bioenergetic data, all in real time.  While this instrument has been around for roughly ten years, it had been relegated to niche fields and saw relatively little exposure.  In fact, many of you may not be aware that Tufts recently purchased one (a Seahorse XFe96, in case you were wondering)!  With more labs and fields now considering the details of cell metabolism within the framework of their research, the Seahorse XF Analyzer (or “Seahorse”, for short) has become something of a gold standard when discussing cellular metabolism profiles and nutrient preference.  With the addition of a Seahorse analyzer to Sackler, now is as good a time as any to consider adding this instrument to your toolbox.

At this point you may be thinking, “Dan, Judi, this all sounds great, but what exactly does it do?” Good question!  Let’s discuss what exactly the Seahorse XF Analyzer measures and how it does so.  Principally, the Seahorse investigates the balance of mitochondrial oxidative phosphorylation and glycolysis within a population of cells.  The instrument is loaded with a stacked double plate.  The lower plate is a relatively simple multi-well plate that the researcher seeds with the cells of study.  The cells form a monolayer along the bottom with a small volume of media on top.  The upper plate consists of probes for each well and four small-volume drug ports per well where the researcher can preload the compounds of interest in order to test the cells’ metabolic response.  The instrument is programmed to inject specific drug ports at precise times and the well-specific probes are lowered into the media to form a microchamber where pH and oxygen level within the media can be measured.  Changes in pH and oxygen level are a consequence of the cells undergoing metabolic processes in response to the drug treatment.  The analyzer can then calculate the rate of change in these parameters, resulting in Extracellular Acidification Rate (ECAR) and Oxygen Consumption Rate (OCR), respectively. These parameters are indicative of how fast glycolysis and mitochondrial oxidative phosphorylation metabolic pathways are working.

With Seahorse, the most important part of your assay will be determining what question you want to ask.  Because of its sensitivity and capabilities, it is very easy to get lost in the amount of data you are collecting.  To aid you in your research, Agilent has a variety of kits available that can answer common questions, and their representatives are more than happy to work with you to develop a custom assay to fit your needs.  Each kit supplies a pre-measured amount of certain drugs, which are injected into wells during the assay.

Questions Assay
  • Are my cells undergoing a metabolic switch?
  • How much proton efflux is due to glycolysis?
Glycolytic Rate Assay
  • How are key mitochondrial parameters changing in my cells?
Cell Mito Stress Test
  • What is the baseline metabolic phenotype of my cells?
  • What is the metabolic potential of my cells?
Cell Energy Phenotype Test
  • What type of fuel (glucose, glutamine, fatty acids) is preferred by my cells?
  • How flexible are my cells toward using other fuels when the preferred fuel is unavailable?
Mito Fuel Flex Test
  • How capable are my cells of using glycolysis when oxidative phosphorylation is blocked?
Glycolysis Stress Test

Additional information can be found at Agilent’s site: http://www.agilent.com/en-us/products/cell-analysis-(seahorse)/seahorse-analyzers?sh_0015

Michael Irwin, MD, to deliver 42nd Charlton Lecture, Oct 25

The 42nd annual Charlton lecture will be held on Wednesday, October 25, 4-5.30 pm, in the Sackler DeBlois Auditorium. The lectureship, established in 1975 in honor of Mr. Earle P. Charlton, has since evolved to include a poster competition that serves as a platform to recognize outstanding research work performed by graduate and professional students on the medical school campus. This year, the poster competition will be held on Tuesday, October 24 and Wednesday, October 25 in Sackler 114. 

The keynote lecture will be delivered by Dr. Michael Irwin, the Norman Cousins Professor of Psychiatry and Biobehavioral Science  at UCLA Geffen School of Medicine, Director of the Cousins Center for Psychoneuroimmunology at the UCLA Semel Institute, Director of the Mindful Awareness Research Center at the UCLA Semel Institute, and Director of the Center’s Inflammatory Biology Core. 

Mr. Earle P. Charlton was a renowned entrepreneur and a social benefactor, as exemplified by his legacy, the Charlton Trust. Mr. Charlton established a chain of stores throughout Massachusetts back in 1890, before merging with the Woolworth company and expanding to the west and Canada. The Woolworth company would later go on to acquire several brands throughout the twentieth century. However, due to increased competition in the retail sector, the company chose to focus on a select brands and is today represented by the Foot Locker stores. Mr. Charlton passed away in 1930, and is commemorated by the Charlton Memorial Hospital in Fall River, MA, a town which benefitted greatly from his entrepreneurship and generosity. (Source – https://en.wikipedia.org/wiki/E._P._Charlton_%26_Company)

About the Speaker

Dr. Michael Irwin, the Norman Cousins Professor of Psychiatry and Biobehavioral Science  at UCLA Geffen School of Medicine, Director of the Cousins Center for Psychoneuroimmunology at the UCLA Semel Institute, Director of the Mindful Awareness Research Center at the UCLA Semel Institute, and Director of the Center’s Inflammatory Biology Core. His ongoing work is focused on the “reciprocal interactions between the immune- and central nervous systems, and the role of sleep disturbance on the molecular and cellular inflammatory signaling pathways that influence depression- and physical health risk with a focus on cancer survivors and older adults” (source). 

Dr. Irwin is best known for his pioneering studies that showed the relation between stress and the hypothalamic-pituitary-adrenal (HPA) axis, and the immune system through receptor activation mediated mechanisms. He also showed that b-adrenergic receptors played a major role in inflammation and anti-viral immunity in a variety of disease conditions ranging from physiological to psychosomatic ones. His broad range of work integrates data at various levels of biological investigation – from the mechanistic details of signaling pathways to epidemiological data and clinical case studies. He is also the recipient of a large number of awards for his ground-breaking work. More details on his work can be found here

Notes from the Library…Open Access

Open Access

In honor of international open access week, which is October 23-29th, I decided to devote this month’s column to demystifying open access.

What is open access?

According to the Scholarly Publishing and Academic Resources Coalition (SPARC), open access is the “free, immediate, online availability of research articles coupled with the rights to use these articles fully in the digital environment.”

What does this actually mean?

Open access removes the legal, financial and technical barriers to reading, downloading and reusing research articles.

While open access publishing models vary, SPARC considers the terms of the Creative Commons Attribution license (CC BY), the standard for open access.  This license grants users the right to share and adapt the material for any purpose, including commercial, provided they properly attribute the authors.  Several major open access publishers, including BioMed Central and PLoS, apply the CC BY license to the articles that they publish.

How can I make my article open access?

There are two primary mechanism by which you can make an article open access: submit your article to either an exclusive (all content open access) or hybrid (some content open access) open access journal; or deposit your final peer-reviewed manuscript in an institutional or discipline repository, such as PubMed Central.  The latter option can only be done with the permission of the journal that has accepted your article for publication.  This can be written into your author’s agreement.

Some open access journal charge authors an article processing charge (APC).  These charges allow the journal to cover the costs of publishing, and range from hundreds to thousands of dollars.  Reputable open access journals collect APCs only after an article has been peer-reviewed and accepted for publication.  Many funders allow grant funds to be used to cover the cost of publishing in an open access journal.

Tufts Libraries have memberships with select open access publishers and journals; Tufts authors who publish in these journals can receive a discount on their APCs.  For more information, see OA Support at Tufts.

Why would I pay to publish in an open access journal?

Open access expands your audience by allowing anyone, not just those who are willing or able to pay for a journal subscription or individual article, to read your article.  A broad audience means your work receives more recognition, and may be used in novel ways that you did not anticipate.

Where can I learn more about open access publishing and choosing a journal for my manuscript?

For more information about choosing where to publish, including resources to evaluate open access journals, see ‘Where to Publish’ in our Measuring Research Impact guide, or contact me (laura.pavlech@tufts.edu).