Repeat Visitor: Diego Rodriguez Terrones

Meet Diego Rodriguez Terrones of Helmholtz Zentrum München (Munich, Germany). The Mexican national is a third-year PhD student supervised by Prof. Dr. Maria-Elena Torres-Padilla from the Helmholtz Zentrum München, and Dr. Juan Manuel Vaquerizas from the Max Planck Institute of Molecular Biomedicine. Diego made his CSHL debut this year and did so with quite the “bang”: first presenting a poster at the Transposable Elements meeting then the Advanced Sequencing Technologies & Applications course less than 48 hours later. We reached out to Diego to ask him of his experiences and if there were any other CSHL meetings or courses on his radar (and we may be welcoming him again for the Mouse Development, Stem Cells & Cancer and the Synthetic Biology courses!). We began by talking about his work and how he made it the focus of his research:

In the lab, we aim to understand the molecular basis of mammalian totipotency, which is the capacity of a single cell to give rise to an entire organism. For example, in the mouse, the one cell of the 1-cell embryo and each of the two cells from the 2-cell embryo are the only three totipotent cells that occur during development. What this essentially means is that if you let a 1-cell embryo develop to term you will get one mouse, and if you split up the 2 cells from the 2-cell embryo and let them develop independently, you will get two twin mice. Once the two cells from the 2-cell stage embryo divide once more to form the 4-cell stage embryo, totipotency is lost and it won’t be possible to initiate development from a single cell ever again during this round of development! Our goal is to understand what makes this particular set of three cells stand out from all others; specifically how the unique epigenetic landscape that arises at the beginning of development mediates this unique totipotent capacity.

Overview of mouse pre-impantation development. Image provided by Diego Rodriguez Terrones

Early on in my career, I realized that my main interests laid within the field of synthetic biology and that my long-term goal was to enable the engineering of biological systems that possess properties or exhibit behaviors not found in nature. However, I also understood at the time that any attempt to engineer life would most certainly fail without a thorough understanding of gene regulation, and all the epigenomic mechanisms that translate one unique genotype into the multitude of cellular phenotypes that exist throughout an organism. Under that logic, what better place to start than the early embryo where the mammalian developmental program and its epigenome are kick-started.

How did your scientific journey begin?

Actually, as far back as I can remember I’ve always wanted to be a scientist! When I was around 5 years old, for some reason, I started watching a lot of astronomy documentaries on TV and became absolutely fascinated by the idea of space exploration. Over the course of the next several years, however, I think I started to understand just how difficult space exploration really was, how little we were doing it, and just how much our biological limitations stood in the way of making space exploration a reality. Mainly because of this, and by the age of 12, I remember having had decided that I wanted to pursue a career in something involving biology or medicine, and was what eventually led me to start a career in genomics during my undergrad.

You recently joined the 200+ alumni of the Advanced Sequencing Technologies & Applications course. What attracted you to the course and what did you take away from it?

Advanced Sequencing Technologies & Applications Class of 2018

I was particularly interested in learning about the new long read sequencing technologies, and about genome assembly and the analysis of structural variants. These two topics were indeed two of the course’s central themes this year, so it was quite productive for me! I think it’s a fantastic course for primarily developing your bioinformatic skills, targeted towards the very latest technologies. I’m happy to have acquired a rather wide collection of new experimental and bioinformatic skills during this course, ranging from variant calling and genome assembly, all the way up to the preparation of single-cell RNA-seq libraries with 10X genomics. I’m in the process of incorporating the training in the analysis of RNA-seq data that I acquired at the course towards my current research project. If anything, I guess my key takeaway from this course -- of this year -- is that long read sequencing technologies are revolutionizing genomics! I think both beginner and intermediate bioinformatic users would benefit from the course equally, which is rather unusual for a course like this and speaks highly about its quality.

This year, you also attended the Transposable Elements meeting. Can you tell us what led you to register for this meeting in particular?

Diego at one of the 2018 Transposable Elements’ poster sessions.

Since I will be finishing my PhD relatively soon, I wanted to see where the field was heading and gather some ideas for my postdoctoral project. As a matter of fact, quite a few of the things that I learnt during the meeting are going to shape what I end up doing during my postdoc. This meeting represents ones of the best opportunities to get a global overview of the transposon field; so if you are working on repetitive elements, I would most definitely recommend it. Another group that I think would greatly benefit from it is anyone working on molecular biology or -omics method development: there are so many crazy molecular mechanisms going on with transposons that I think it would be rather inspiring!

One key takeaway was very neatly put forward by Cedric Feschotte during his keynote when he argued that the genome can only be understood as an ecosystem. I think this concept very elegantly puts together the idea that genomes are teeming with all sorts of selfish genetic entities that range from DNA transposon and endogenous retroviruses, all the way to parasitic repetitive elements that exploit other transposable elements for their own replication. However, the key point here is that while this interplay between host genome and transposable elements can give rise to genetic conflicts, it can also result in selective advantages to the host organism by providing a continuous source of novel regulatory sequences and even of novel regulatory proteins.

Since you’ve now experienced both meeting and course life at CSHL, did you pick up any differences or similarities between the two function types?

Well, long hours are definitely a constant between both!

What did you like most about your time at CSHL?

The course materials are perhaps my favorite general thing. They are of exceptional quality and permit us to come back to them for further reference once we start applying what we learnt! Also, the instructors were great, and it was really easy to approach them to discuss how to best address the specific challenges we are encountering in our own projects.

During the meeting, I really enjoyed the poster session. The quality of the posters were remarkable and there were tons of posters I was extremely interested in visiting! Fortunately, there was also a lot of time to mingle around during the poster session which is definitely not the case at every meeting). Also, the keynotes were spectacular!

Thank you to Diego for sharing with us his experience, and we look forward to having him back at the Laboratory again for the two courses he has his sights set on - Mouse Development, Stem Cells & Cancer and Synthetic Biology. Both annual courses are accepting applications until March 1, 2019 and April 1, 2019, respectively. The Advanced Sequencing Technologies & Applications course will again be offered at CSHL from November 5-17, 2019 (with applications due here by July 15, 2019); and the Transposable Elements meeting will return in October 2020.

Also, we would like to particularly thank Prof. Torres-Padilla, his institutions, HELENA (Helmholtz Graduate School Environmental Health), and Chromatin Dynamics (Integrated Research Training Group IRTG-SFB 1064) for providing Diego with the financial support that enabled him to participate at his CSHL meetings and courses this year.

To meet other featured scientists - and discover the wide range of science that takes part in a CSHL meeting or course - go here and here.

Repeat Visitor: Pau Creixell

Photo provided by Pau Creixell

Pau Creixell of the Koch Institute for Integrative Cancer Research at MIT is the next scientist to be featured in the 2018 edition of our Repeat Visitor series. Pau is a postdoctoral fellow in Michael Yaffe’s lab, which is part of the MIT Center Precision Cancer Medicine. In the thirteen months since October 2017, Pau trained in three of our courses: X-Ray Methods in Structural Biology, Workshop on Leadership in Bioscience, and Scientific Writing Retreat. And with the Network Biology meeting and courses on Cryoelectron Microscopy and Synthetic Biology in his sights, we will likely be seeing Pau again. In the meantime, we reached out to Pau to discuss his experiences so far and learn what keeps him coming back to Cold Spring Harbor.

Talk us through your research interests and how you made them the focus of your work.

Using both computational and experimental quantitative approaches, I am interested in understanding how specific cancer mutations perturb protein function and cause disease. The focus of my work is protein kinases, a subset of proteins highly mutated in cancer and targeted by many therapeutic agents. I find cellular signaling and protein kinases fascinating because even though they have been studied for decades, we are still discovering new molecular functions for them and learning how they are perturbed in cancer. The degree of regulation and functional diversification in protein kinases is very interesting to me, and the amount of sequencing and functional information that we have for them now allows for more systematic studies. It’s a field that has repeatedly shown how fundamental discoveries in molecular biology can lead to effective targeted therapies that benefit patients.

How did your scientific journey begin?

When I was young, a family member was diagnosed with cancer and that had a big impact on me. Since then, I decided that by doing research I could try to contribute to our understanding of the disease which, in turn, could result in better therapies. I was also very fortunate to have a supportive home and school environment, where my curiosity was encouraged by my parents, grandparents, and teachers.

As I was finishing my undergraduate studies in biology, the Human Genome Project was being completed and a number of cancer genome projects were starting. I quickly realized that to address fundamental biological questions, we would need to not only generate quantitative data, but also integrate and decode large and diverse sources of data. This inspired me to pursue a PhD in computational systems biology. Since my ultimate goal is to lead an interdisciplinary lab, I wanted to complement my computational training with expertise in cancer biology. Thus for my postdoc, I purposely transitioned into a lab where I could improve my experimental skills in biochemistry and molecular/cellular cancer biology.

Your most recent course at CSHL was last month’s Scientific Writing Retreat. Can you tell us what attracted you to the retreat?

Scientific Writing Retreat Class of 2018

Given the time scientists invest in writing and the number of versions every manuscript, grant, or application goes through, I always felt that the process of writing could be improved and made more enjoyable. I wanted to learn more about scientific writing in general and how the process may change depending on the purpose of each document. A major takeaway from the retreat is to focus on the audience and how it will interpret your writing. The audience is often broader and more diverse than most of us appreciate; keeping this in mind ensures that key information is presented clearly and your writing is easy to understand.

Since part of the retreat is devoted to practicing on your own work, I returned from it with much-improved versions of abstracts for two manuscripts as well as a research statement. I also learned how to give better feedback on the scientific documents of others, and I increased my understanding of how scientific stories are crafted, submitted, and published. I picked up general writing strategies (e.g., given the limited space in titles, abstracts, and summaries, one has to use the most meaningful words and avoid superfluous ones) and became aware of my major writing weakness (referred to as “your kryptonite” in the retreat). Communicating your science effectively is required to become a successful scientist, and I would like to thank the great instructors, coaches, and my fellow participants for their help.

It’s becoming more common for trainees of the Scientific Writing Retreat to also participate in the Workshop on Leadership in Bioscience. In fact, you are among six recent alums who participated in both the retreat and leadership workshop. Was there something specific about the leadership workshop that led you to apply for it?

I think it is no coincidence that several trainees attend both the leadership workshop and writing retreat as these skills are critical for those transitioning to scientific independence.

I have found there to be little leadership training for scientists, who are supposed to run labs without any formal training on how to successfully manage and lead others. Similar to how I looked for both computational and experimental training opportunities during my PhD and postdoc, I attended the leadership workshop because, in my mind, it was important to be as prepared as possible if I want to effectively lead my own interdisciplinary laboratory in the future.

Workshop on Leadership in Bioscience Class of 2018

Generally speaking, any starting junior faculty will want to set up an exciting, fun, and creative lab environment but, as covered in the workshop, this will ultimately depend on hiring the right people and setting the right lab environment and expectations. Another important takeaway from the workshop is to recognize that no one is infallible and everyone makes mistakes when running a lab. You have to be open to feedback from everyone and ready to learn from your own mistakes so you can fix them as soon as they are detected. By establishing consistent and objective parameters during the hiring stage and requesting independent feedback from everyone in the lab, one can aim to counteract intrinsic biases and group-thinking, thereby cultivating a diverse and creative lab.

Though I currently have limited opportunities to manage others, I have already implemented some of the aspects I learned and have been working to overcome some of my weaknesses as a leader. The facilitators of the workshop are incredibly knowledgeable and I plan to stay in touch with them as my leadership skills develop. I, along with the facilitators and other workshop participants, have joined a LinkedIn group where we keep in touch and share our ideas.

Finally, the laboratory short course on X-Ray Methods in Structural Biology: Was there something specific that led you to apply for this course?

For my postdoc, I was interested in learning techniques that would allow me to better characterize the molecular effects of mutations in proteins. During a meeting with my PI, he recommended this course, which he himself attended and enjoyed twenty years prior.

From my participation in the course, I took away an appreciation for the physical principles behind x-ray crystallography. It is extremely exciting to be able to learn the fundamentals from those who pioneered the field and developed the technologies and software that are now commonplace. I crystallized many different proteins and learned how to explore different crystallization conditions. I also emerged from the course clearly understanding how diffraction data are interpreted so that structural models can be derived. Being able to transition from raw data to a model and back to the data is an important skill, so that one doesn’t simply take the structural model as the only solution. As I am working on solving structures for protein kinases in complex with specific substrate peptides, this has allowed me to critically evaluate the different research options moving forward. Coming from a computational background, it is also appealing to consider that a research project can now begin by mining millions of cancer somatic mutations, and finish by resolving the molecular differences between mutant and wild-type proteins at atomic resolution.

The overall format of your three courses are different. What differences or similarities did you pick up, and what advice can you share with future participants?

All three of the courses had a direct impact on the way I now look at scientific problems and the scientific process in general. The training was intense but extremely worthwhile, and I learned something new every day. In all cases it also felt like the more effort you put in, the more knowledge you get out, so I would certainly encourage future attendees to complete any assignments that are suggested by the instructors.

An aspect easily overlooked about these courses is that they offer a great opportunity to build community. The topics, formats, duration, location (Banbury versus CSHL main campus), instructors, and attendees were obviously different in the courses I took, but they all had a similar feeling of being part of a community. My memories include laughing and sharing experiences with participants and instructors of diverse origins and backgrounds, going for morning runs together, and relaxing in the basement of Robertson House and on a sailing trip. When one is an early-stage scientist like I am, often competing with peers, it is important to remember that the vast majority of us are driven by shared interests in addressing thought-provoking scientific questions and contributing positively to society.

Pau received financial support from the Convergence Scholars Program, Helen Hay Whitney Foundation, Helmsley Charitable Trust, National Cancer Institute, and National Institute of General Medical Sciences. On behalf of Pau, we would like to thank these organizations and agencies for continuing to support and enable our young scientists to attend a CSHL course where they expand their skills, knowledge, and network.

The three courses Pau took part in - Workshop on Leadership in Bioscience, X-Ray Methods in Structural Biology, and Scientific Writing Retreat - will again be offered at CSHL in 2019. All three courses have already begun to accept applications, and applications for the leadership workshop are due by January 15, 2019 here.

Thank you to Pau for sharing with us his experience, and we look forward to having him back at the Laboratory again. To meet other featured scientists - and discover the wide range of science that takes part in a CSHL meeting or course - go here and here.

Repeat Visitor: Ethan Greenblatt

Photo provided by Ethan Greenblatt

Ethan Greenblatt of the Carnegie Institution for Science continues our 2018 Repeat Visitor series. Ethan is a postdoctoral fellow in Allan Spradling’s lab and, since 2012, has been a regular at the Germ Cells meeting at CSHL. His successive participation has enabled him to “see how projects evolve over time and what new ideas and themes come up.” This year, he again took part in Germ Cells and trained at the Drosophila Neurobiology: Genes, Circuits & Behavior course (fly course). Ethan already has plans to attend the 2020 meeting on Germ Cells so we reached out to learn more about what keeps him coming back to campus.

Tell us about your research and how you decided to make it the focus of your research?

Oocytes have an extraordinary ability to go into a “deep sleep” like arrest state for decades - human oocytes, for example, are produced during fetal development and can remain functional for up to five decades. I am interested in how oocytes control their gene expression, understanding which genes work together to keep oocytes healthy, and what eventually goes wrong that leads to age-onset infertility. The idea to study this specific question came over the course of many conversations with my advisor when I first joined this lab. This research question ties together my interests in aging and the lab’s expertise in female germ cell biology.

How did your scientific journey begin?

I was always interested in science (especially physics and astronomy) but when it came to actually doing the science, I found biology labs incredibly interesting places to be. I started my career by volunteering in the lab of the late James Dvorak at the National Institutes of Health. He taught me that there are so many fundamental questions in biology that remain unanswered and that even an individual researcher in biology can make a major advance by doing well thought-out experiments.

Ethan at one of the 2018 Germ Cells’ poster sessions.

Since 2012, you have attended three Germ Cells meetings – what is it about this particular meeting that keeps you coming back?

The CSHL Germ Cells meeting is one of the best in the field, and I have enjoyed the extremely high-quality research going on in a multitude of model organisms. I was particularly excited to get a chance to discuss our recent research findings and learn how the frontiers of germ cell biology are evolving. The field is in the good hands of many passionate and talented researchers. These meetings are also not overwhelmingly large which gives you wonderful opportunities to interact with participants. I’ve gotten the chance to meet incredibly valuable colleagues and collaborators in the future. I had a chance to talk with many experts at an early stage in my project when I presented a poster in the 2014 meeting. The feedback I received gave me inspiration, energy, and motivation to keep on pursuing the questions I posed at the meeting.

Was there something specific about the fly course that led you to apply for it in particular?

We discovered that many of the genes that keep oocytes healthy are also required for proper neural development and function. In particular, a gene called FMR1 is linked to important autism spectrum as well as reproductive disorders. The commonality may be because synapses and oocytes use similar mechanisms to control when and where genes are expressed. I wanted to get a deeper background in neuroscience so that I might one day be able to directly connect my findings of how genes - like FMR1 - work in oocytes to understand how they help neural synapses function.

Drosophila Neurobiology Class of 2018

What was your key takeaway from the fly course and what advice would you impart to those interested in this course?

My key takeaway from this course was that the Drosophila neuroscience community is incredibly welcoming and supportive and that eventually doing simple neuroscience experiments in my future lab might not be as crazy an idea as I initially thought. I would love to eventually be able to test the role of oocyte genes in synaptic plasticity and homeostasis using some of the many methods I learned from the course.

My advice would be that if you’re considering the course to do it. You will be exposed to an incredible range of ideas and techniques, high quality instructors, and the hands-on curriculum will enable you to try out experiments in the lab at CSHL that you might not even know are possible.

Now that you’ve experienced both meeting and course life at CSHL, did you pick up any differences between the two function types?

The experiences of attending a CSHL course and meeting were quite different for me. The CSHL meeting is intense in a different way: a lot of great talks and late night discussions, and an amazing opportunity to present my research to the field. The meeting had the feeling of an amazing get-together with colleagues and friends from around the world; whereas, I loved the chance to feel like a student in an unfamiliar area of science during the three-week course. I loved working late into the night trying out all of the different neuroscience techniques we were learning. Many students would stay in the lab until midnight almost every night, and the instructors and students felt like a kind of family by the end of the course. CSHL became like a home.

What did you like most about your times at CSHL?

My favorite thing about the course as well as the Germ Cells meetings were the relationships I developed. At the course, it was with instructors, teaching assistants, and fellow students. Similarly, I had amazing interactions with fellow researchers in my field at the meetings.

The Drosophila Neurobiology: Genes, Circuits & Behavior course will again be offered at CSHL from June 28 to July 18, 2019; and applications are being accepted here until March 15, 2019.

Thank you to Ethan for sharing with us his experience, and we look forward to having him back at the Laboratory again. To meet other featured scientists - and discover the wide range of science that takes part in a CSHL meeting or course - go here and here.

* Ethan received a fellowship from the Helmsley Charitable Trust to cover a portion of his course tuition. On behalf of Ethan, thank you to the Helmsley Charitable Trust for supporting and enabling scientists to attend a CSHL course where they expand their skills, knowledge, and network.

Repeat Visitor: Leila Rieder

Photo provided by Leila Rieder

The next scientist to be featured in the 2018 edition of our Repeat Visitor series is Leila Rieder. Leila is a K99 postdoctoral fellow in Erica Larschan’s lab in Brown University with a visiting appointment at Princeton University. And, next April, she will take on her new role as Assistant Professor in the Biology Department of Emory University. Leila made her CSHL Meetings & Courses debut in August 2017 when she trained at the Proteomics course. She returned for this year’s Quantitative Imaging: From Acquisition to Analysis course (QICM) followed by a poster presentation at the Nuclear Organization & Function meeting a few weeks later. We caught up with Leila to chat about her experience at our meetings and courses, and if she has any plans of participating in a near future meeting or course.

Tell us about your research interests and how you decided to make it the focus of your research.

I’m most interested in how genes are coordinately regulated -- turned on and off at the same time. Cells are remarkably good at this and we don’t know how they do it! I first began by focusing on how sex chromosomes are singled out for unique regulation, a process called dosage compensation. In these systems, basically all the genes carried on a single chromosome are coordinately regulated. However, it’s not simply the chromosomal location that leads to this coordinated regulation; there are other signals. While researching the role of a known dosage compensation protein on the male X-chromosome, I discovered the same protein was involved in regulating another group of coordinated genes: the histones. These genes are often clustered together within genomes and are notable and unique for many reasons. Every time a cell divides, it needs a huge output of histone proteins in the right ratios so they are incredibly important genes!

How did your scientific journey begin?

My father is a cell biologist and, to be honest, because it was important to me to forge my own path, I tried very hard to be anything other than a biologist! But because of my father’s research, I spent my childhood summers at the Marine Biological Laboratory and sat through so many meals where the entertainment (the entire conversation!) was dominated by my father and his colleagues debating their newest results. They couldn’t get together without “talking science” and I wanted to have those conversations myself -- and now I do!

Quantitative Imaging: From Acquisition to Analysis Class of 2018

This year, we hosted 26 meetings and 34 courses - how did you narrow down which ones to attend?

I taught myself most of the microscopy I know, and was intensely aware that I was probably doing 50% of it incorrectly. (After the course, I realized I was closer to 90%.) I knew that if I wanted to perform experiments correctly, I needed formal guidance and a background in theory. I’ll soon be in a position to guide my trainees through their own research, and will make sure to never suggest they do sloppy or ignorant microscopy!

As for the meeting, I decided it was important to understand how my favorite genes and loci were situated in the nucleus. I had been working in the field of coordinated gene regulation but without deeply considering higher-order organization and genomic context.

What is your key takeaway from QICM? Also, what advice would you give to someone interested in this course?

Quantitative microscopy is incredibly powerful when used correctly, but there are many ways to use it to find false positives and red herrings. Most of all, I will never apply a quantitative microscopy technique without first researching all the ways in which it can go wrong. I think the best time to take this course is when you have some basic microscopy experience but haven’t yet significantly applied it to your biological question. Be prepared to hear about the different ways your past experiments were sub-par. It’s not a great feeling, but it’s better to learn sooner rather than later!

For Nuclear Organization & Function, what feedback can you provide for those interested in participating in its 2020 iteration?

Leila during her poster presentation at the 2018 Nuclear Organization & Function meeting.

The field of nuclear organization and function is much broader than I imagined! It focused on specific topics that were not as relevant to my work as I had expected but, due to it, I now read more broadly. The meeting itself is a great opportunity to meet people—both those who are everyday names as well as those you might not have heard of but are doing really interesting work. I presented a poster entitled “Dynamic identification of the dosage-compensated Drosophila male X-chromosome during early embryogenesis,” and the experience was intense, as many poster sessions are, but friendly. I liked that the meeting was small so it was neither difficult to find people nor for them to find me.

Since you’ve experienced both meeting and course life at CSHL, did you notice any differences or similarities between the two function types?

Since you basically live and work with your course mates for two straight weeks, you really get to know them. We come from so many backgrounds and different countries, and are using what we learn during the course for wildly different purposes. This diversity really adds to the experience. This is all true of the meeting participants as well, but you don’t get to know them to the same extent since the meetings are only four days long.

Our readers are always eager to learn of ways to fund registration. Can you share how you were able to fund your CSHL meeting and course participation?

Since I am located at Brown and Princeton Universities - neither of which are far from CSHL - transportation to CSHL is easier and less costly for me than for most. For tuition and registration support, I received small grants from my home institution, NCI for QICM, and CSHL generously delayed payment for the course tuition until my K99 grant was available. I was also provided tuition support by NICHD when I took the Proteomics course in 2017.

What did you like most about your experience at CSHL?

Overall, I enjoyed meeting so many interesting people from backgrounds so different than mine. At the meeting, what I liked the most was the chance to sit next to someone new at dinner. As for the course, the instructors, TA’s, and vendors were really fantastic and you can absolutely tell they love teaching the course—they live and breathe it even more than the students do! And they had boundless energy. They never got tired of answering questions and, when the students finally shuffled out at the end of a long evening, they stayed to set up for the next day. They are amazing!

Do you have a future CSHL course or meeting on your radar?

Yes! Now that I am about to begin my own research group, I plan on taking the Workshop on Leadership in Biosciences this coming March. And, someday if I have time, I’d like to take the Programming for Biology course. I’m also planning to attend the Mechanisms of Eukaryotic Transcription meeting in 2019.

Both the Quantitative Imaging: From Acquisition to Analysis and Proteomics courses will return to the Laboratory in 2019; and applications are already being accepted. Apply to QICM by January 31, 2019 here, and to Proteomics by April 1, 2019 here.

Thank you to Leila for sharing with us her experience, and we look forward to having her back at the Laboratory again. To meet other featured scientists - and discover the wide range of science that takes part in a CSHL meeting or course - go here and here.

Repeat Visitor: Tatiana Schnieder

Among the ~9,000 scientists we hosted this year, a number of them participated in multiple meetings and/or courses. Kicking off the 2018 edition of our Repeat Visitor series is Tatiana Schnieder, an assistant professor of clinical neurobiology at Columbia University and an adjunct assistant professor at Hunter College. Tatiana divides her work between two research labs – the neuropathology laboratory of Dr. Andrew Dwork at Columbia University Irvin Medical Center and epigenetics laboratory of Dr. Fatemeh G. Haghighi at Mount Sinai School of Medicine. This year, Tatiana took part in the 83rd CSHL Symposium on Quantitative Biology and joined the ranks of both the CSHL Protein course (Expression, Purification, & Analysis of Proteins & Protein Complexes) and The Genome Access Course (TGAC). Previously, she presented a poster during the Glia in Health & Disease meeting in 2016 as well as attended Blood Brain Barrier that same year. We reached out to Tatiana to chat with her about her experiences in CSHL meetings and courses, and to learn more about what keeps her coming back to campus.

Tell us about your research interests.

My research is focused on the question of brain-periphery interactions in psychiatric disorders. To be more specific, I am currently investigating whether or not the reported relationship between suicide and central and peripheral inflammation is mediated by changes in blood-brain barrier (BBB) permeability.

How did you decide to make this the focus of your research?

During my doctoral training, I investigated prefrontal white matter microglia in individuals who died by suicide; and although I did not find any significant differences in microglial activation between suicides and non-suicides, suicide decedents had significantly higher densities of juxtavascular phagocytic cells in dorsal white matter than diagnostically-matched non-suicide decedents. Interestingly, however, studies of animal models of psychiatric symptoms have attributed maladaptive behavior in rodents to peripheral inflammation and to the influx of peripheral immune cells into the brain parenchyma. These findings and my own findings in postmortem human brains prompted me to investigate the involvement of peripheral immune cells in pathology associated with completed suicide. Further research revealed that non-parenchymal immune cells do not contribute to the increase in perivascular cell density that we observed in suicide; which suggests that resident microglial cells -- rather than non-parenchymal immune cells -- cross-communicate immune responses between the periphery and central nervous system in suicide. Moreover, those who died by suicide had a lower surface area density of microvessels in dorsal white matter -- the same brain region where I found increased densities of perivascular phagocytes. Cumulatively, these findings indicated that changes in the properties of the neurovascular unit could be contributing to pathological changes that lead to suicide. This piqued my interest in the role of BBB in psychiatric disorders. The goal of my current project is to determine if completed suicide is associated with transcriptional, epigenetic, or protein changes in the neurovascular unit.

Expression, Purification & Analysis of Protein & Protein Complexes Class of 2018

What led you to apply for the Protein course and how has it contributed to your work?

I applied to the Protein course to find answers to the challenges I faced during the preparation of my samples for HPLC/mass spectrometry. To assess changes in the expression level of key proteins crucial for BBB function and identify novel differentially expressed proteins, I use HPLC/mass spectrometry proteomics to interrogate protein expression profiles in isolated microvessels. To investigate BBB changes in psychiatric disorders and suicide specifically, I wanted to optimize a microvessel isolation protocol from postmortem frozen human tissue. It was important for me to develop the best method for the extraction of cytosolic, membrane, and transmembrane proteins that seal a gap between the brain endothelial cells. The two-week course gave me a lot of hands-on practice in protein isolation and, through extensive communication with the Instructors and use of the course materials, I was able to come up with the optimal protocol for my project. My main takeaway from the course is that it is imperative to learn as much as possible about your protein/s of interest before you start your experiments. Know your target well because what may work for one protein can be detrimental to another.

How about TGAC? Why did you register for it and what is your key takeaway?

My BBB project involves data that will require knowledge of bioinformatics, and I want to understand what goes into the analyses of the data I produce at the bench. I took TGAC to start learning how to analyze high-throughput data obtained using next-generation sequencing methods and mass spectrometry. As for my key takeaway: Apply what you learn in the course without delay. To acquire a new skill, one needs to practice often – if not daily – therefore it is important to “play” with your data so as to avoid forgetting what you pick up from the course.

The two courses have very different formats: the Protein course consists of hands-on training in a laboratory setting while The Genome Access Course is purely computational. What can you share about the differences or similarities between your experiences in the two courses?

The Genome Access Course Class of 2018 (Spring)

The two courses I took were indeed very different: TGAC was a short two-day course, whereas Protein course was two weeks long and so requires a completely different level of commitment. What is expected of you is also different: TGAC course is mostly lecture-based with some hands-on computer work, and the Protein course is mostly lab-based with lectures sprinkled throughout the day and evening. You cannot really choose to opt out, and by the end of the first week you already feel like you are a part of a team. In fact, working in a team and as a team will be the main mode of learning in a longer course. Irrespective of which course you decide to take, you will be taught by the top experts in the field within a friendly and supportive learning environment, where you will always have the ability to discuss and clarify concepts that may be confusing. It was an amazing experience: I was challenged to step out of my comfort zone, which is how personal and professional growth happens.

The focus of the CSHL Symposium changes annually. This year its topic was “Brains & Behavior: Order & Disorder in the Nervous System,” with an emphasis on neuroscience and related technologies. Besides the overall topic, what attracted you to participate in it?

Once you graduate, it is easy to focus on your specific area of research and, sometimes, you lose sight of the bigger picture. I strive to prevent this from happening to me. As a college professor, I need to stay abreast of the new discoveries in the field of brain research, and attending the Symposium was a perfect way to catch up with the latest findings. It provided a diverse range of topics and speakers from top-notch brain research labs. When this Symposium hones in on this topic again, I would recommend aspiring neuroscientists to attend. If you haven’t yet decided what you want to dedicate your research to or are looking to expand your network, this is a great conference.

Since you’ve now experienced both meeting and course life at CSHL, what differences or similarities did you notice about the two program types?

The courses had a much more focused agenda and required a few prerequisites so you are more likely to meet people who share similar professional or academic experiences as you. The meetings, on the other hand, were eclectic and brought together people from very diverse backgrounds. But in both instances, expect to be surrounded by like-minded people enthusiastic about science and the discoveries it brings.

What did you like most about your meeting and courses this year?

I am very lucky to live a short train ride away from CSHL. Since the first CSHL meeting I attended in 2016 on Glia in Health and Disease, I keep coming back because the quality of the meetings and courses have always been stellar, and the content and organization of the events always meet my expectations. In fact, I am looking forward to attending the Blood Brain Barrier meeting in 2019.

Both the Protein course and TGAC will return to the Laboratory in 2019; and applications are already being accepted. Apply to the Protein course by January 31, 2019 here.

Thank you to Tatiana for sharing with us her experience, and we look forward to having her back at the Laboratory again. To meet other featured scientists - and discover the wide range of science that takes part in a CSHL meeting or course - go here and here.