Repeat Visitor: Diego Rodriguez Terrones

Photo provided by Ethan Greenblatt

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

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

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.

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

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

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

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.

Visitor of the Week: Oscar Perez

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Meet Oscar Perez, director of the Developmental Biology Laboratory 113 in the Pontificia Universidad Católica del Ecuador’s School of Biological Sciences, a graduate student in Dr. Federico Brown’s lab at the University of Sao Paulo, and the Ecuadorian representative in the Latin American Society for Development Biology Board. Oscar was on campus for two courses this year – Scientific Writing Retreat followed by Computational Genomics – but his history with CSHL started twelve years ago when he took his first CSHL course. We caught up with him to ask what keeps him coming back.

What are your research interests? What are you working on?
I am interested in the evolutionary comparison of reproductive strategies and early development of Ecuadorian chordates. My research is currently focused in the plasticity of oocyte organization and how this can modify the embryological events. I apply the comparative method in order to find molecular variations in oogenesis and embryogenesis of the Ecuadorian megadiverse fauna.

How did you decide to make this the focus of your research?
Since an early age, I was always interested in nature and I was fortunate to have a childhood surrounded by forests and open fields. I clearly remember hearing the Quito frogs singing in the cold nights and looking for bugs under the stones in the morning. I have to thank my mother for showing me a marvelous chicken birth and what I consider my very first exposure to embryology. Every child should have a similar opportunity.

How did your scientific journey begin?
I had the great fortune of working with great mentors with Dr. Eugenia del Pino, Dr. Richard Elinson, and Dr. Luis Coloma being the most influential to my scientific formation. I became extremely interested in embryological events while working with the outstanding Ecuadorian embryologist Dr. Eugenia del Pino. In her lab, I had the opportunity to be involved – for the first time – in the diverse and fascinating area of embryology by studying the embryos of Ecuadorian frogs which began my fascination for this almost unknown field of biology. My love for molecular techniques, evolution, and direct development came from Dr. Elinson’s expertise, and my passion for reproductive biology and ecology came from scientific interaction with the brilliant herpetologist Dr. Luis Coloma.

Was there something specific about the Computational Genomics course that drew you to apply?
There were three main reasons I applied for the Computational Genomics course in CSHL: 1) My previous experience in the CSHL Xenopus and live imaging training courses were brilliant; 2) The outstanding instructors listed for the genomics course; and 3) CSHL is considered one of the most prestigious scientific institutes in the world.

What and/or how will you apply what you've learned from the course to your work?
Undoubtedly, all the information I acquired from the course will be of great help in my research and institution. I have to say that my research in the non-model science world. Ecuadorian alternative models such as frogs, ascidians, and sea slugs do not have standardized molecular tools as in mice, Xenopus, or the human. Fortunately, in this course I learned of alternative ways to take advantage of modern computational tools to analyze transcriptomic data from my non-model species and still get informative results despite the absence of reference genomes and other existing tools that are easily obtained in human and mouse. Institutionally, my Computational Genomics training is very important because these skills can be shared with other laboratories and groups in collaborative investigations.

What is your key takeaway from the course?
The take-home message from the Computational Genomics course is that genomics is a flexible tool that can offer several alternative strategies to solve one single question. The experience of the genomics experts and mentors were extremely useful to learn how to effectively extract many hidden results from your data.

If someone curious in attending this course asked you for feedback or advice on it, what would you tell him/her?
My answer would say to complete all the homework sent by the instructors before the course. Even when you are not required to be an expert in the field, you must have a certain level of knowledge in order to get in the fast lane of learning. Also, bring data. If you have an unsolved problem in this regard, the Computational Genomics course is the right place to solve it.

How many CSHL courses have you attended?
Computational Genomics, 2018
Scientific Writing Retreat, 2018
Immunocytochemistry, In Situ Hybridization & Live Cell Imaging, 2009
Cell & Developmental Biology of Xenopus, 2006

Thinking back on your course at CSHL (Cell & Developmental Biology of Xenopus in 2006), did you notice differences or similarities between that course and Computational Genomics?
I still clearly remember how intense and diverse the training was at the Xenopus course in 2006 and, even after 12 years, that same level intensity and high quality of the courses in CSHL has remained the same. Although, considering the tasks sent weeks before the course started, preparation of a poster, and the mid-term test, I could even say that Computational Genomics might be more demanding than the 2006 course.

Since your first two CSHL courses, your career stage has changed. Given your present position, did your experience in the course change in any way?
Course features such as intensity and quality of the knowledge offered are contrastable; however, it is without doubt that CSHL offers first-rate courses instructed by leaders in the field of science. Over the years, my capacity of appreciating this knowledge has evolved. When I was a younger researcher, I did not fully appreciate how great an opportunity it was to train and be trained in one the most prestigious scientific institutes in the world. But, as my experience has expanded, I have become more aware of the magnitude of having opportunities to learn and to learn from such a source.

What do you like most about your time at CSHL?
The confidence that you acquire by mastering specific techniques. The rate of learning in CSHL is very high as is the demand and complexity of the courses. It is great to have the opportunity to ask your questions to pioneers, leaders, and scientific experts that collaborate with CSHL to teach and share their knowledge. 

Oscar received a fellowship from Pontificia Universidad Catolica del Ecuador (PUCE). On behalf of Oscar, thank you to the PUCE for supporting and enabling our scientists to attend a CSHL course where they expand their skills, knowledge, and network.

Thank you to Oscar for being this week's featured visitor. To meet other featured scientists - and discover the wide range of science that takes part in a CSHL meeting or course - go here.

Repeat Visitor: Ethan Greenblatt

Photo provided by 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.

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

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.

Visitor of the Week: Paul Marcogliese

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Meet Paul Marcogliese of Baylor College of Medicine (BCM) and the Jan and Dan Duncan Neurological Institute. He is a postdoctoral associate in HHMI Investigator Hugo Bellen’s lab within the Department of Molecular and Human Genetics of BCM. Paul was on campus for the tenth Neurodegenerative Diseases: Biology & Therapeutics meeting where he presented a poster entitled: “Loss-of-function variants in IRF2BPL are associated with neurological phenotypes”.

What are your research interests? What are you working on?
I am interested in the use of model organisms, particularly the fruit fly, to functionally assess candidate disease causing genes in human neurological disease; specifically, unraveling the molecular and cellular pathogenic mechanisms driving neuronal cell death in two movement disorders: IRF2BPL-linked neuroregression and Parkinson’s disease.

How did you decide to make this the focus of your research?
We are in the era of genomic sequencing that is progressing towards what has been called ‘personalized or precision medicine’. However, the identification of disease causing variants (even with access to large control databases) can be a challenge in light of the amount of natural genetic variation and variation of unknown significance. To bridge this gap, we can use genetically tractable model organisms, like the fruit fly, to help the human genetics diagnosis effort. Humanization strategies in model organisms that allow the functional assessment of a candidate disease variant and compare it to the human reference gene can support disease diagnosis and shed insight on biology. Added to this, the brain and its related disorders still remain a substantial challenge to understand. I feel that model organisms can be used in identifying and unraveling the function of genes causing these disorders. This will also lead to the identification of therapeutic targets thus helping both patients and families.

How did your scientific journey begin?
It has been an interesting journey for me. After completing a BA in criminology at 23 years old, I went to adult high school to complete 3 science credits that I initially avoided. This was due to an increasing interest in science primarily through understanding the evolutionary mechanisms underlying the diversity of life. Then, while completing a BSc in forensics, I was fortunate to work in the lab of David Park at the University of Ottawa studying animal models of Parkinson’s disease. It was here where my love of the scientific process really developed and what led me to conducting my doctoral studies in the Park lab. Not only did I work on mouse and fly models of Parkinson’s disease, but I met inspiring patients.

Now that I am a postdoc in the Bellen lab, I get to be part a large collaborative effort: the Undiagnosed Diseases Network (UDN). The UDN employs next-generation sequencing and model organism studies to help diagnose individuals with rare, undefined diseases. Our newly discovered human disease gene, IRF2BPL (Marcogliese et al., AJHG, 2018), which we originally deposited to bioRxiv has led to meeting a handful of patient families that inspire me to determine a more mechanistic understanding of the gene/disease in hopes of potential therapy.

Was there something specific about Neurodegenerative Diseases: Biology & Therapeutics meeting that drew you to attend?
I have kept a high interest in the role of glia in the pathogenesis of neurodegenerative disorders. There was a substantial portion of the meeting focused on this topic. Additionally, as part of a team studying rare diseases, it was important for me to be able to present our recent work identifying IRF2BPL-linked neuroregression to this audience. While the audience may be focused on more common neurodegenerative diseases, their input and advice on tackling novel diseases/genes will only help.

What is your key takeaway from the meeting?
Not all neurons are the same and there is differential susceptibility across neurodegenerative diseases. Additionally, glial cells -- specifically microglia -- are clearly critical players in neurodegenerative disease development and progression. Hence, from a therapeutic standpoint, there are multiple cell types and potential targets to ameliorate or slow disease progression.

What did you pick up or learn from the meeting that you plan to apply to your work?
The Bellen lab excels at model organism work in vivo, but the CSH meeting has allowed me to make collaborative connections with experts in the iPSC field that could allow us to translate our findings to human cells.

If someone curious in attending a future iteration of this meeting asked you for feedback or advice on it, what would you tell him/her?
I would tell them it was a great experience. The two main reasons why I enjoy CSHL meetings are that the topics are focused enough to attract major players in the field to attend, and there is a substantial discussion of unpublished and novel ideas in the field.

What do you like most about your time at CSHL?
CSHL is located on a beautiful campus. The smaller size of the meeting allows for an intimate atmosphere where everyone is very approachable and inclusive. It not only builds networks but also friendships.

Thank you to Paul for being this week's featured visitor. To meet other featured scientists - and discover the wide range of science that takes part in a CSHL meeting or course - go here.