Visitor of the Week: Paul Marcogliese

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.

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.

Visitor of the Week: Tatiana Moiseeva

Meet Tatiana Moiseeva of the University of Pittsburgh. The Russian national is a postdoctoral associate in Dr. Christopher Bakkenist’s lab. She returned to campus for her first CSHL course: Scientific Writing Retreat.

What are your research interests? What are you working on?
I study how human cells initiate the replication of their DNA and how they suppress the majority of the available replication origins that should only be used in the event of stress. Certain drugs that are currently in clinical trials can induce excessive replication initiation and make cells more prone to toxic DNA damage.

How did you decide to make this the focus of your research?
I have always been interested in basic science questions. The Bakkenist lab focuses on using certain kinase inhibitors to sensitize cancer cells to ionizing radiation, and we found an unexpected effect of a drug that was supposed to be inert in the absence of DNA damage. My natural curiosity took over and I had to figure out what happens exactly, and it turned out that I can use this drug to answer some basic science questions, so I couldn’t resist.

How did your scientific journey begin?
I completed my undergraduate and graduate degrees in St. Petersburg, Russia. I had amazing professors in the Polytechnical University who inspired me, encouraged discussion, critical thinking, taught me the importance of constant self-education, and really shaped my scientific mind. Doing research in Russia was not easy but they, by example, showed me that nothing is impossible if you put your mind to it. I have switched a few research topics since then, but I think my education is what defined my scientific path.

Was there something specific about the Scientific Writing Retreat course that drew you to apply?
Scientific writing is a critical part of working in academia. To date, I have written multiple manuscripts and grant proposals that I asked my PIs to look over. They always provided feedback but they weren’t always able explain why I should write something in a certain way. My goal in attending this course is to become more independent in my writing and improve this valuable skill for future work as an independent researcher.

What and/or how will you apply what you've learned from the course to your work?
Ask several people to read your text before submitting it. Getting feedback, even from non-experts, can help a lot.

What is your key takeaway from the course?
For any piece of scientific writing, proper structure is key. Whether it is a seven-figure paper or three-sentence abstract, the order of the messages is what matters the most.

How many CSHL courses have you attended? How about meetings at CSHL?
This is my first course but I am very curious about the Workshop on Leadership in Bioscience. I attended the Cell Cycle meeting in 2012 and DNA Replication meetings in 2015 and 2017. I am planning to attend the 2019 Eukaryotic DNA Replication & Genome Maintenance meeting.

If someone curious in attending this course asked you for feedback or advice on it, what would you tell him/her?
This course is very useful, informative, and intensive. Before coming to the retreat, think about the general and specific writing problems you are having because the time at the retreat is very tight. Anything can be solved, you will see the progress immediately. Also, the course is always the week before Thanksgiving - be ready for the snow!

What do you like most about your time at CSHL?
A chance to meet new people from very different backgrounds (that we don’t really get at scientific conferences), learn about their experiences and make new friends. Also, very good dinners. 

Thank you to Tatiana 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: 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.