This month I present, for your reading pleasure, excerpts from my interview with Nafis Hasan from CMDB. Nafis and I had a remarkably wide-ranging conversation covering existential philosophy, cultural differences between Bangladesh and the US, the exquisite symmetry between ecology and cell biology, and current controversies in carcinogenesis research. I can only hope to capture in the space below a mere whisper of his deeply-considered intellectual convictions and passion for social justice. Fortunately, Nafis has also authored an editorial on Science Activism in this very issue, and I strongly urge you, dear reader, to check that out next!
Having a grand time in Dhaka
AH: Where did you grow up?
NH: I grew up in the house that my father and his brothers built in Dhaka, Bangladesh, and moved to the U.S. when I was 18. Most of my dad’s siblings and their families lived with us in Dhaka. As kids, we didn’t really have the notion of “privacy” for the longest time: the elders would each get a room and the kids would sleep in the living room on a big mattress. My cousins and I would all get into trouble at the same time… it was fun!
On the road with college friends
AH: Have you had any opportunities to travel around the States?
NH: For F1 visa (student visa) holders, you have a 3-month window where you have to find a job or get into school. After graduating from Lafayette College [in Easton, Pennsylvania], I thought, “If I have to leave the country, I might as well see it.” So when one of my friends said, “Let’s do a road trip,” I said “Let’s do it!” We started from Pennsylvania, went down to Virginia, our first stop was Shenandoah – I had actually never been camping before that, it was all a very new experience. We had two American kids, a Colombian kid, and a kid from South Africa… It was very liberating, and I started to see the country as it really is. At the same time, on the road, I was interviewing for jobs. I remember doing a job interview [by video phone] at a McDonalds in Idaho. I borrowed a shirt from one of my friends who dresses nicer than I do, since the interviewer could only see the top half of me… Over the course of two months, I think I applied to 200 jobs. Finally, I ended up getting a research tech job at Thomas Jefferson University in Philly.
Basking in the beauty of nature at Yellowstone
AH: What was it like adjusting to American culture?
NH: When I came to America, I had no idea what to expect, I had only heard things from my cousins who came here for college and what was on TV. One thing that I had in my mind was that I was going to try and meet as many people of different nationalities as I can. But there was a big cultural divide, how they grew up versus how I grew up. I think the road trip really helped me to understand the diversity of American people and especially during these times when people are so polarized, I reach out to that experience. We grew up seeing this version of America as the land of opportunity, the land of freedom, but America is not the government, is not their foreign policy, is not the consumerism that has taken over the world… America is more about the people that you meet here, and that’s how I see the country. America encapsulates the dichotomy of homogeneity versus heterogeneity, and I think that’s so beautiful.
The scholar/activist as a young man
AH: When did you begin to discover your interest in biology research?
NH: In Bangladesh I went to a private school that taught everything in English. The division of sciences starts in 7th grade, and biology was definitely the most interesting to me. At the same time, I was caught up in the process of deconstructing my religious identity, because I was reading biology which has hard facts about how your body works, which calls into question how life was created… I found that more fascinating than having a set answer imposed by some superior being.
Positive work environment!
AH: How did you choose your field of study for grad school, and why is it so interesting?
NH: I started reading a lot of scientific nonfiction, presenting cancer as a very complex biological phenomenon, which was fascinating to me. I also had a solid foundation in breast cancer by the time I applied for grad school and I wanted to pursue that… I had seen lots of tumors, but no mammary glands. The more I learn about the mammary gland, the more I am fascinated by it. It develops throughout life: initially it’s just a branched structure that looks like sticks; when you get pregnant, it almost flowers, with grape-like clusters that come up through alveologenesis and these alveoli then revert back to the branched structure after weaning. It’s comparable to how trees shed leaves in the Fall, except in reverse: this course of nature – the seasons that you see – the same dynamic is there in animal tissue. And all of this is happening through the lifetime, after the majority of the organs are already fully developed!
First Century – Repping Sackler at 2015 Tufts Century Ride
AH: What is one of the big challenges or controversies in your field at the moment?
NH: Traditionally, cell culture is done in two dimensions, on plates that are usually plastic – and plastic is not a natural substrate for cells to grow on, so you can’t recapitulate the same 3D environment where the cells are growing inside an organism. You can either try to mimic the natural environment as much as possible, or try to make a scaffold that is biocompatible… Cells need to be able to manipulate their environment, just as the environment should be able to provide them with physical or chemical cues to make them grow or organize in certain ways. Our lab has a very organic approach to it: we do 3D cultures in type 1 collagen, the predominant structural protein found in the mammary gland stroma. We believe that “organicism is greater than reductionism.” This is where we’re at odds with a lot of others in the cancer field, where reductionism is still the predominant philosophy. And we’re not saying it’s bad! It’s just insufficient to explain carcinogenesis.
Science is often thought of as a monolithic entity, but it is actually a complex composition of a discipline, an institution, and a community, all focused on finding truth and knowledge in data and the natural world. Science as a community consists of people of all ethnicities and from all socioeconomic classes; talent is found everywhere, and we as scientists do not and should not limit our number to those with a privileged pedigree. Science as an institution is a pillar of modern society, supporting and enabling growth and progress previously impossible to achieve. Science as a discipline is an investigative practice that demands rigor, critical analysis, and substantive evidence to support the conclusions that we draw from the data. Science as a discipline to formulate theory may be apolitical, but as an institution and a community that is an integral part of modern civic society, science cannot simply be an idle observer. Atrocities have been committed in the name of science when the idea of the pure monolith prevails and is exploited by political regimes to suppress minorities, such as the Tuskegee syphilis experiments and Nazi human trials. However, science has also been used to fight for the welfare of all people and to resist such regimes: Rachel Carson, Albert Einstein, Linus Pauling, Max von Laue all used their privilege as scientists to fight for justice and the greater good. While the scientific discipline provides a path for pure theory, we are human, each with our own biases that guide our investigation, influence our analysis, and may even blind us to the truth. Ultimately, the application of scientific theory to society bears the imprint of our ideas and our biases, and we as a community bear responsibility for the results. It is therefore imperative that we distinguish the apolitical discipline of science from the institution and community of science, which are a part of civic society and inherently political. We currently hold privileged positions in society that are at risk in the contemporary political climate. The defense of science is our moral and civic duty. Furthermore, in defending ourselves, we should also take a stand to give a voice to those who cannot do so for themselves.
This is not a temporary issue. Trump is not the only President who has or will challenge evidence-based policy and threaten the scientific community. However, it is crucial that we take action now because the dangers of climate change are imminent and we cannot afford to deny it anymore. Therefore, it is imperative that scientists come forward to educate and communicate with the public in a language and tone sufficient to start a dialogue. We start by communicating with each other, educating each other about our work. From there, we communicate and educate our family members and relatives, our friends, our communities and beyond. This has to be a grassroots movement – no top-down policy will fix the scientific literacy issue and lead American society toward a future where policies are based on hard evidence as opposed to blind faith. This is how we can give back to the public, who provide the majority of funding for our work, and ensure that science does not belong to an elite population, but in the hands and minds of the people.
This is why we are calling on you, each and every scientist, ranging from technicians to postdocs, graduate students to faculty, to action. Educate and communicate with your science. Explain why it is necessary. Even if you talk to just one person a day, that can make a difference. That is where we start. If you want to do more, organize. Rally behind policymakers who heed scientific evidence and will champion such causes. Volunteer at high schools and colleges. Take part in science festivals. Celebrate science and its achievements sans the elitism. It is not about funding, or whose research is more important. It is about making science accessible to the masses, who have tirelessly supported and benefited from our work for decades and will continue to do so. It is about rescuing science from the clutches of political partisanship. It is about freedom to communicate our science, the protection of our community, and the advancement of our society.
For too long academics have been cooped up in their self-imposed exclusive isolation from the masses. For too long we have assumed that Science exists in a vacuum. We cannot afford this axiom anymore. We have to consider the social, political, and economic forces that affect the direction of scientific research. We have a moral and civic duty to fight for what is right and to prevent the use of science to advance fascist ideology. The time to take action is now.
Here are some resources to help you take action in the short term –
Above all, talk to your family. Talk to your friends. Tell them about your work and explain why it is necessary for science to overcome partisan politics. Help educate the younger generation on the importance of scientific research. And last but not least, thank them for their support for your work.If you know of any other actions/events taking place to support Science, please let us know by leaving a comment on this post.
Here at Maine Medical Center Research Institute, we are very happy to be supporting Tufts trainees and working with many Tufts investigators here and in Boston to provide core facility services such as transgenic mouse generation.
Did you know that many of our core facilities were established at Maine Medical Center through a special NIH program, the Institutional Development Award (IDeA) Program? The IDeA program was established by Congressional mandate in 1993 to help develop research infrastructure to support biomedical research in 23 states that historically have had a low level of NIH funding. Maine is one of those states. In fact, there was a time when 50% of NIH funding went to researchers in 5 states (Massachusetts being one of those heavily funded states!), while the 23 IDeA eligible states together only received about 5% of all NIH funds. Over the last 23 years, NIH investment in biomedical research in Maine has contributed to a burgeoning biotech scene (http://www.mainebioscience.org/access_resources/bioscience-map-of-maine/) and a highly collaborative network of research institutes.
One of the components of the IDeA program is the Centers of Biomedical Research Excellence (COBRE). Maine Medical Center has been fortunate to have received two COBRE awards since 2000, one with the theme of Vascular Biology, and one in Stem and Progenitor Cell Biology. These awards have supported the recruitment of new junior investigators to Maine Medical Center (with appointments at Tufts University School of Medicine), and also the establishment and expansion of our core facilities. Please visit our website at mmcri.org, and find “Core Facilities” under “Research Services & Resources” to see if we provide services that could be useful to your research!
Microinjection of mouse fertilized oocyte. Our Mouse Transgenic Facility performs genome modification using standard transgenesis, gene targeting in ES cells, or CRISPR/Cas. In 2017, we will start to offer services for CRISPR/Cas project design and sgRNA synthesis.
Imaging by microCT. We run a Scanco vivaCT40 for microCT imaging of bone, teeth, fat, and the vasculature. Image, above right, shows microfil perfusion of the vasculature of a tumor xenograft, used to quantify and measure tumor angiogenesis.
Proteomics and Lipidomics Core Facility. We run a mass spectrometry resource with state-of-the-art protein and lipid profiling capacity. Recent studies include experiments to study tissues including adipose tissues and the skeleton, and how their protein and lipid content changes during metabolic disease.
Histopathology Core Facility. We provide full services for tissue processing, embedding, sectioning, routine histology, and immunostaining. We work closely with our Maine Medical Center Biobank to generate tissue arrays for screening of human disease specimens from patients.
In January 2015, President Obama announced the launch of the “Precision Medicine Initiative”, proclaiming it to usher in “a new era of medicine that makes sure new jobs and new industries and new lifesaving treatments for diseases are created right here in the United States.” In addition, he remarked that the promise of this initiative laid in “delivering the right treatments, at the right time, every time to the right person”. This initiative, with bipartisan support in the Congress, provided a total of $215 million investment in 2016 for the NIH, along with the FDA and the Office of the National Coordinator for Health Information Technology (ONC), with a large portion of the money ($70 million) awarded to NCI to “scale up efforts to identify genomic drivers in cancer and apply that knowledge in the development of more effective approaches to cancer treatment”. The initiative doesn’t stop at the genome level, as Dr. Francis Collins, Director of the NIH, pointed out in an interview with PBS News Hour, and is meant to provide information about environmental exposures, lifestyle choices and habits and pretty much everything that can affect one’s health. Given the mass of information that will be generated (the initiative aims to enlist 1 million volunteers for its cohort), it is no surprise that patient privacy issues, as well as database infrastructure, are major concerns in this mammoth undertaking.
In addition to this initiative, the US government also launched its “Cancer Moonshot Program” a year later in January 2016. This program, under the leadership of Vice President Joe Biden, and with the help of an expert panel, the “Cancer Moonshot Task Force”, aims to “make more therapies available to more patients, while also improving our ability to prevent cancer and detect it at an early stage.” Since cancer is widely accepted to be a genetic disease, it seems fitting to serve as the poster child for an initiative that aims to cure and prevent diseases based on tailoring therapy for an individual using personal genetic information.
Tied to these two initiatives is also the latest approach to clinical trials at the NCI, commonly termed as “basket trials”. Based on findings from exceptional case reports where patients treated with drugs not commonly used for that type of cancer, the NCI was encouraged to try out drugs traditionally reserved for particular types of cancer for the ones that they weren’t developed for; thus, the Molecular Analysis for Therapy Choice (MATCH) and the Molecular Profiling-Based Assignment of Cancer Therapy (MPACT) trials were incorporated into the Precision Medicine initiative. The NCI-MATCH trial aims to sequence tumor biopsy specimens from ~6,000 patients to identify mutations that will respond to targeted drugs selected for the trial; these drugs are already approved by the FDA for certain cancer types or are being tested in other clinical trials. On the other hand, the MPACT trial will compare whether patients with solid tumors fare better with targeted therapy vs non-targeted therapy.
The NCI-MATCH trial explained. Source: National Cancer Institute website.
Despite the initial fanfare, the recently released NCI-MATCH major interim analysis report does not paint a pretty picture for the trial’s outcome. While the enrollment was higher than expected (795 people registered in first 3 months compared to the projected 50 patients/month) and the labs were able to sequence most of the tumors (87%), it was also found that “most of the actual mutation prevalence rates were much lower than expected based on estimates from The Cancer Genome Atlas and other sources”. In fact, the overall expected mutation match rate was adjusted to 23% for the 24 treatment arms in the study as it continues.
While no endpoint has yet been reached to draw conclusive remarks about this trial, data available from other clinical trials that have taken a similar approach do not seem favorable. In the SHIVA trial, a randomized phase II trial carried out in France where 99 patients were treated based on identified mutation(s) compared to 96 patients treated with drugs of their physicians’ choice, median progression-free survival was 2.3 and 2 months, respectively. Current clinical data on patients with relapsed cancers, a major focus of the MATCH trial, do not seem favorable either. As Dr. Vinay Prasad, a haematologist-oncologist at Knight Cancer Institute, points out, only 30% of such patients respond to drugs based on biological markers and the median progression-free survival is 5.7 months. Based on this response rate, he estimated only 1.5% of patients with relapsed and refractory solid tumors to benefit from the precision medicine approach.
In a review of current clinical trials and past trials that have used the targeted therapy approach, Tannock & Hickman (NEJM, 2016) warn about the limitations of such an approach – heterogeneity and clonal evolution of cancer cells when challenged with targeted therapy, the inconsistency between expected and clinically achievable levels of inhibition of candidate molecules and of course, the efficacy of such therapies compared to currently available, standard but effective therapies such as aromatase inhibitors for breast cancer. While one can argue that heterogeneity in tumors can be countered with combination targeted therapy, the authors point out that “combinations of molecular targeted agents that target different pathways have often resulted in dose reduction because of toxic effects… in a review of 95 doublet combinations in 144 trials, approximately 50% of the combinations could use the full doses that were recommended for use as single agents, whereas other doublets required substantial dose reductions.” Even if it is possible that intratumoral heterogeneity can be countered with combination targeted therapy, a much-overlooked point in this initiative is the cost of such treatment strategy, considering the exorbitant costs of targeted cancer therapy. There already exists a disparity among cancer patients from a socio-economic standpoint and this initiative does little to address how to bridge such a gap. Questions such as how many drugs will a patient have to take, especially in cases of tumors that are highly heterogeneous, such as glioblastoma multiforme and how that would affect the living standard of a patient need to be considered before heralding a victory for the precision oncology approach even if the MATCH trial outcomes are favorable.
In another recent study, Dr. Victor Velculescu and his team from Johns Hopkins showed that sequencing only tumor genetic data can lead to false positives. After analyzing 815 cancer patients’ tumor sequencing data and comparing that data to the one from the patients’ healthy tissue, they found that 65% of genetic changes identified with tumor-only sequencing data were unrelated to the cancer and therefore, “false positives”. The team also found that 33% of mutations, which are targets of currently available drugs, were also false positives when the patient’s germline genome was compared to the tumor genome; this affected 48% of the patients in their cohort.
The paradigm behind the MATCH trial, and in general the Precision Medicine initiative, seems to be blind to an obvious aspect of biology – context matters, and more so, in case of mutations that are deemed to be “carcinogenic”. As outlined in a recent paper by Zhu et al (Cell, 2016) and the famous “bad luck” paper by Tomasetti and Vogelstein, it appears that the stem cells and their differential regenerative properties in different tissue types are responsible for the differential rates of carcinogenesis in various tissue types, a finding that again, buttresses the idea that tissue specificity matters. In fact, Iorio et al (Cell, 2016) was able to show just that in the context of pharmacogenomic interactions of currently available cancer drugs with data available from patient samples in the TCGA and other databases. Using a big data and machine learning approach, the authors developed a logic-based model that would predict the efficacy of any drug that is either approved or undergoing clinical trials against the mutation it is intended for in different cancer types ,which is essentially the basis of the MATCH trial. Surprisingly, it appeared that tissue specificity determined the pharmacological agents’ effects on the intended molecular targets; more specifically, only one drug interaction (out of 265 drugs tested) was found to be significant in multiple cancer types, which may sober up the expectations from the MATCH trial outcome. Therefore, using a blanket approach to target mutations in various tissue types without consideration to their environments can seem futile in the light of such findings.
The evidence from all these basic science and clinical studies raise the question of whether precision medicine is doomed to fail. While the gene-centric view of disease etiology have deepened over the years since the completion of the Human Genome Project, does this evidence point to the necessity of another paradigm in our understanding of cancer and other complex diseases, whose cures have been presumed to lie in genetic aberrations and molecular targets? An even more concerning question, relevant in this era of big data, is whether we actually understand what the data is telling us, as the prominent cancer researcher, Dr. Robert Weinberg, admits that “while data mining, as it’s now called, occassionally flags one or another highly interesting gene or protein, the use of entire data sets to rationalize how and why a cancer cell behaves as it does is still far beyond our reach”. A strong critic of the initiative, Dr. Michael Joyner from Mayo Clinic, opines that while “hundreds of genetic risk variants with small effects have been identified…But for widespread diseases like diabetes, heart disease and most cancers, no clear genetic story has emerged for a vast majority of cases” and that “when higher-risk genetic variants are found, their predictive power is frequently dependent on environment, culture and behavior”.
The success of Precision Medicine Initiative, and in particular, the precision oncology approach, ultimately rests on whether it can stem and curb deaths resulting from cancer and other complex diseases, based on molecular targeted therapy. Unfortunately, it appears that large scale public health initiatives have done more to that end (e.g. – tobacco control has largely cut down rates of lung cancer incidence, diet and exercise can cut down the risk of converting pre-diabetes to diabetes by nearly two-thirds), compared to what targeted therapy have achieved. However, it seems that such public health success was overlooked by the Cancer Moonshot panel as in February 2016, right after the program was announced, public health researchers across the country had to urge the Vice President to make prevention a bigger focus in controlling cancer incidence in the population, rather than just trying to find a cure. This approach should have been incorporated into a billion-dollar initiative by default, one would think, but this didn’t seem to be the case and one must wonder why.
In order for this huge, publicly-funded initiative to achieve more than just lukewarm outcomes and to actually become a breakthrough it is promised to be, the Precision Medicine initiative needs to break free of the gene-centered tunnel vision and incorporate all factors that affect an individual’s health, such as lifestyle choices and environmental exposures, as Dr. Collins boasted it to be. While this initiative is only at its infantile stage, changes based on clinical trial and basic science evidence should be made early enough so that favorable outcomes can be achieved and does not require the government to stage another public bailout as it did for the failing banks and wall street corporations back in 2008 when they were deemed to be “too big to fail”.
We often get asked about what statistical and data analysis programs are installed on the library’s computers, or available for installation on personal computers. Here is a summary of the computers available at the Hirsh Health Sciences Library, and a chart indicating which statistical and data analysis programs are installed on these computers and available to students:
Public Computers: Desktop computers on the 4th and 5th floors of the Sackler; available for anyone to use.
Computers labs: Desktop computers in Sackler 510 and 514; available for use when not reserved for a class (check schedule on white board behind Tufts Technology Service Desk on 5th floor of Sackler). All computers in both labs were recently replaced.
Laptops: Mac and PC laptops available for checkout at the Library Service Desk on the 4th floor of Sackler; available for students, faculty and staff to checkout for 4 hours.
The 41st annual Charlton lecture will be held on Wednesday, November 30, 4-5.30 pm, in the Sackler 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, November 29 and Wednesday, November 30 in Sackler 114. Details regarding participation, eligibility and review criteria can be found here – http://sackler.tufts.edu/Student-Life/Student-Awards/Charlton-Poster-Award. The deadline for submitting abstracts for the competition is Thursday, Nov. 9, 5 pm. Please submit your abstracts electronically to Rachael Bailey at Rachael.Bailey@tufts.edu.
The keynote lecture will be delivered by Dr. Tyler Jacks, Professor of Biology at Massachusetts Institute of Technology (MIT) and Director of the David H. Koch Institute for Integrative Cancer Research. His talk is titled “Engineering the Cancer Genome”.
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. Tyler Jacks is the Professor of Biology at MIT, the Director of the David H. Koch Institute for Integrative Cancer Research and a Howard Hughes Medical Investigator. He has served on public and private advisory panels on cancer research and also sits on the board of directors for Aveo Oncology and Thermo Fisher, Inc. His expertise in the field is of no surprise given his pedigree – Dr. Jacks completed his PhD under the guidance of Nobel Laureate Dr. Harold Varmus at University of California, San Francisco, and went on to do his postdoctoral work with Dr. Robert Weinberg at the Whitehead Institute, both of whom were pioneers of the field. His work has earned him prestigious awards including the Paul Marks Prize for Cancer Research and other accolades.
Dr. Jacks’ research focuses on the “genetic events contributing to the development of cancer” using mouse models that have been engineered to carry clinically relevant mutations. His lab works on a number of different cancers that range from lung, pancreatic and ovarian cancers to peripheral nervous system tumors, astrocytoma and retinoblastoma. A major focus of his current research is to develop more powerful and accurate mouse models of cancer using cutting edge genetic technology.
More detailed information regarding his work can be found on his lab website.
What is NMR?
Nuclear magnetic resonance spectroscopy, or NMR spectroscopy, is a powerful technique that uses the magnetic properties of atomic nuclei to elucidate the chemical and physical properties of the atom or its molecule. The nuclei of certain atoms, such as 1H or 13C, align themselves with magnetic fields in nuclear energy levels known as ‘spin states.’ When molecules are placed in an external magnetic field and irradiated with radiofrequency (RF) waves, certain atomic nuclei present in the sample absorb energy. These RF waves flip nuclei from one spin state to another. If the RF is turned off, the nuclei relax, releasing energy in the form of RF waves, which are measured as the decay in signal intensity over the course of a few seconds. The time domain of these signals is converted to the frequency domain to produce a spectrum, what we normally think of as the output of an NMR experiment.
But what can you actually do with NMR? Traditionally, the technique has been used to identify molecules and determine their 3D structures. It can certainly do this; however, the actual range of applications for this technique is much wider. With metabolomics approaches, you can quantify biofluids and tumor and tissue extracts. Binding events, even very weak ones, between two proteins or between protein and DNA can be detected. You can also determine the stoichiometry of these binding events. Trying to compare a wild-type protein to its mutant variant? Characterizing the active site of your protein of interest? NMR can handle both of these tasks, and measure dynamics of the protein in its active conformation as well. To that end, NMR can also be used in live-animal imaging. If you’ve ever had an MRI, you may know that the technique is actually based on the science of NMR!
Figure 1. 1H-15N 2D spectrum of BPV-1 E2 DBD (310-410). Resonances of the DNA-bound protein (red) show chemical shift differences relative to the DNA-free sample (black) (taken from Veeraraghavan et al. Biochemistry (1999) 38: 16115-16124).
What facilities does Tufts have for NMR spectroscopy?
The Tufts NMR Center currently has 3 NMR spectrometers, all located in an environmentally controlled laboratory on the 6th floor of M&V.
The Bruker DRX-600 spectrometer used for structure determination of large protein domains and small proteins, as well as metabolomics experiments. It offers the highest resolution and sensitivity of the three instruments.
The Bruker AMX-500 spectrometer is good for examining peptides and small protein domains.
The Bruker DPX-300 spectrometer is useful if you need to check the identify or purity of products of organic synthesis. The system is set up to look at nonstandard nuclei, such as 11B.
The NMR Center is also in the process of upgrading the Bruker DRX-600 by replacing the console electronics. With this upgrade, features such as non-uniform sampling and cryogenic cooling, which can double the sensitivity of 2D and 3D experiments. Other upgrades to the hardware will increase the reliability, ease of use, and speed of data collection for this system. Users will be able to study the structure and dynamics of proteins and protein complexes with high molecular weights and limited solubility, which is limited by the current sensitivity of the instrument.
If you are interested in reading more about NMR spectroscopy, Bothwell and Griffin wrote a straightforward but in-depth article (Biological Reviews (2011) 86: 493-510).
The Diversity and Inclusion page of the Tufts website includes colorful bar graphs on the university population. Sackler is 62% female and over 15 different countries are represented. Much beauty can be found in exploring our diversity, but much can be also gained from learning what unifies. Here at Sackler, many of us study this unity.
My research focuses on the disease of epilepsy, but I find the work rewarding and worthwhile because of the potential to find common mechanisms on how human brains work. Many unifying discoveries on the human system have come from study of disease. Take the textbook case of Patient HM, who had both sides of his temporal lobe surgically reduced to cure his epilepsy. Through studying him during learning tasks, Dr. Brenda Milner demonstrated in the 1950s the existence of episodic and procedural memory. In neuroscience today, cognition and consciousness are two remaining Holy-Grails, and both are affected in epilepsy. Epileptic individuals often suffer from cognitive disorders. In studying consciousness, investigators such as Dr. Hal Blumenfeld at Yale have used the transient impairments of consciousness observed in epilepsy to discover a “consciousness system” network in the functioning brain. The study of disease unveils the nature of the working machine.
Many different diseases are studied at Sackler, but looking at the big picture, what many of us are engaged upon is a search for unifying truths about the human condition. We are creating knowledge of what unifies. If you discover one truth, one singular truth of how the human body works, it is a truth that applies to all, to every group represented on the Tufts Diversity and Inclusion page. This is an empowering thought.
Remember student council elections in high school? Typically the most popular student running would win, but everyone was full of enthusiasm and excitement to attain those coveted positions! Fast-forward a decade or so to filling positions in organizations like the student council during graduate school and the picture looks dramatically different. We each take a turn, but we tend to do so grudgingly. High school was grueling, don’t get me wrong, but as the years progress the demands on our time change, the expectations are different, and the student body is less diverse (no more Poli Sci majors to eagerly take on the class president position).
Organizations that support fellow trainees and coworkers are typically run by volunteers. Each year we need people with a fresh perspective to step up and help with maintaining organizations such as the Graduate Student Council, the Sackler InSight, the Post-Doc Association, and, up here in Maine, the Research Fellows Association. There are so many important career and social events that just would not happen if these organizations were to disappear, not to mention how much smaller our voice within the school would be.
If you find yourself holding back from taking part in one of these community serving groups because you simply don’t have time between experiments, think of participation as a convenient way to get some career development in. Those of us who have been shoehorned into leadership positions can tell you firsthand how much rigorous practice we get in using the “soft skills”. In the business vernacular these include but are not limited to social and emotional intelligence, ability to develop people, delegation, structure and tactile development (how you get stuff done and how you tweak things to make sure it keep s getting done), style flexibility, and focus1.
Experience on a leadership team will create a tangible CV bullet that is particularly important for anyone interested in going into industry, but such experience will also be very helpful for people staying in academia (think committee and ancillary duties). It’s all in how you frame your skills to your audience.
Any of the students currently serving on committees or volunteering in other capacities will be more than happy to share their experiences, what their responsibilities and time commitments have been, contacts they have made, and what they have gotten out of their service in terms of personal and professional development.
For a more in depth explanation on these soft skills, see SciPhD competencies and SCIPHD.com
