Nuclear Organization & Function Meeting

Repeat Visitor: Leila Rieder

Photo provided by 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

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.

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.

A Word From: Edith Heard, Tom Misteli & David Spector

2018-nucleus-meeting-organizers

Earlier this month, Cold Spring Harbor Laboratory hosted the tenth biennial meeting on Nuclear Organization & Function. We sat down with three of the four organizers -- Edith Heard, Tom Misteli, and David Spector -- to chat about how the nucleus continues to stay at the forefront of molecular biology and why this meeting should be on the radar of every specialist. The conversation opened with how the meeting and field have evolved since 1998:

David: When the meeting started, it mostly looked at specific proteins or genes, studying their dynamics in 3D, and learning about the dynamics and interactions of various nuclear bodies. Over the past two decades, the meeting has evolved to where the questions are now more centered on genome-wide analysis, whether it be by chromosome painting, Hi-C, or RNA-Seq techniques. We’re now looking  at the nucleus in a more global sense: how functions take place in the nucleus, how the genome is organized, and how dynamics are altered upon changes in various physiologic states.
Edith: Since I first participated in this meeting in 2006, I have seen the evolution David mentioned. Before, it was still quite descriptive: types of bodies, types of RNAs in the nucleus, etc. There has indeed been a shift to the more genome-wide approaches that look at how chromatin is organized. People are also using all sorts of nice tricks to look at mutants and see whether these bodies, structures, and RNAs matter in more developmental and disease-type situations. And the imaging is just amazing now. It’s extraordinary how far one can go with these super resolution approaches, where the live imaging goes really well with the genomic information. To me, we’re seeing the beginning of a whole new era where we can visualize the 4D aspect of the nucleus. 
Every time we discuss whether we should organize another nucleus meeting, we wonder if maybe things have gone beyond the nucleus. But actually the nucleus keeps being very much at the forefront when it comes to the questions that interest a wide community. 
Tom: I first attended this meeting as a postdoc in 1998 so I see its evolution very differently. What’s the same is the realization that the nucleus is very complicated. I think we’ve made a lot of progress over the last twenty years but it still feels like we’re just scratching the surface. We have much better tools now, there’s no question about it, but it’s interesting that the tools are in a way similar: biochemistry and imaging…
Edith: And genetics.
Tom: And genetics. These have evolved and are now very powerful. Twenty years ago, I don’t think we ever felt we were going to solve this problem but now, because of the tools, there’s hope that we can actually do it. Something that struck me this year was the confluence of people thinking about different things. In the past, it was rare for somebody to talk about chromosomes, and then talk about lamins, proteins, or nuclear bodies. But now people think in a more holistic way. 
David: Unlike most other meetings which focus on one aspect of the biology like chromatin, RNA, or nuclear export, this meeting encompasses all of those areas and more. It’s a more systemic evaluation and study of nuclear organelles, looking at all aspects and how they communicate with each other. It brings people from different fields together and so there’s a lot of cross talk at this meeting that, in and of itself, will provide avenues for advances.

Collectively, David, Edith, and Tom have attended eighteen CSHL Symposia. We were curious to hear their thoughts on the similarities and differences between their meeting and our annual symposium.

Edith: The symposia are one-offs that each explores a different topic, whereas this meeting is about continuity and community. Some of the postdocs who come to the meeting end up as PIs who eventually help run it.
David:  Both have their advantages. The symposia are structured whereby speakers are all invited and are leaders in the field. It’s good to go to a meeting like that because a leader in a particular field will present very differently than a student or postdoc; there’ll be a lot of big picture insights into how the field should move ahead, so there’s a lot to be learned from that type of meeting. Here, the predominant speakers are students and postdocs. That’s also important because it gives them an opportunity to present their data and get exposure to PIs and colleagues. Attending and presenting at this meeting is sort of, in a way, preparation for having their own lab. 

We next asked the organizers who they think should attend this meeting and why:

Tom: This is not a field dominated by a single expertise that will give you all the answers. Not everyone can do everything. So a geneticist probably doesn’t do biophysics, but they need to know the biophysics and that’s why I think this meeting is so important. Even though you yourself are a specialist, learning about other fields that are relevant to what you’re doing is absolutely beneficial. 
Edith: The attendees all come here from different angles. They’re not necessarily nuclear experts, but they clearly share interests in understanding how the nucleus behaves and the influences that can happen in more in vivo settings. 
David: In addition to initiating this meeting, I started a Cold Spring Harbor course called “Immunocytochemistry, In Situ Hybridization & Live Cell Imaging” in the 1990s. The course has evolved over the past 25 years and is now called Quantitative Imaging, but it’s still running. That course and this meeting go hand-in-hanDavid: when those trainees participate in this meeting, they are able to see how the techniques they learned are being applied to answer biological questions.
Edith: Another aspect is that  there aren’t many other nucleus meetings. And so this is a community of people who like to come back to the same place and re-connect with colleagues they met last time. People are attracted to this meeting and Cold Spring Harbor because of the community.
David: As Joe Gall always reminds me, this meeting is the home of the nucleus field. 
Tom: It’s also very focused on students and postdocs. It’s a Cold Spring Harbor tradition to have a lot of postdoc and grad student speakers, so that’s a reason for especially students and postdocs to attend. This is also a great meeting for people who are not directly in the field to learn about the field. We’re seeing a lot of physicists, chemists, engineers who build microscopes, all getting into this field. I think this has something to do with the complexity and diversity of the question. So this is a great place for people to find out what the biological problem is and how they can apply their expertise and contribute. It really takes a village. 
Edith: That’s true, how many other fields have attracted the mathematicians, physicists, and chemists? In biology? Not that many and yet they’re flocking to attack this particular set of biological questions.

We concluded our chat by asking about recent scientific developments they’re most excited about: 

Edith: Right now I’m most excited by the ability to get both genomic and imaging information out of a single cell, and hopefully combine those to really look at the dynamics of nuclear function at every level from the molecule right through to the phenotype. The single cell approaches -- whether it’s imaging or extracting transcriptomes, Hi-C maps, or epigenomes -- the combination of the two is very exciting. You can suddenly see stuff that you suspected (or didn’t suspect!) was there. 
Tom: Related to that, the appreciation of heterogeneity and variability between individual cells is exciting. As we said before, this is a very complex problem and so to study it, you simplify. But we’re beginning to realize that every cell is a little bit different and there’s no one way to organize the chromosomes. Because of technologies like single-cell biochemistry and imaging, we’re going to learn a lot about the fundamental principles of how these biological systems work. I think that’s where we’re going and I find that exciting.
David: I would like to see more work on disorder and plasticity. Most people always think, “This has to be super organized, it has to do this to work.” But I don’t think the cell works that way; from a human evolutionary perspective, that would be very dangerous. So I would like to see more of the general neighborhood that things can take place in, how much leeway is there, and what does it all look like in real cells and tissues, rather than in cultures that have been growing in a dish for 25 years. I think more work in that regard would be extremely insightful. 
Edith: And a kind of hierarchy as well, to ask if a gene in a particular part of the nucleus at a particular time matters. We used to just watch and say, “Oh look it’s there!” But now we can address the question mechanistically and I think that’s amazing. 
David: And “What if it was here, would it still work?” 
Edith: Yes.
Tom: Also, we’ve been so busy looking at the fundamentals that we haven’t really applied the knowledge we have to disease models. We use disease as a model system, as natural experiments, but we haven’t truly explored nuclear structure in the context of disease, or in a systematic and focused manner that you can take into the clinic. There’s a lot to be discovered there.

On behalf of the organizers, we hope to see everyone back at CSHL for the 2020 Nuclear Organization & Function  meeting taking place from April 28 to May 2. 

For more conversations with other meeting organizers, check out the rest of our A Word From series. 

Photo: Constance Brukin

Visitor of the Week: Martin Sztacho

martin-sztacho

Meet Martin Sztacho of the Institute of Molecular Genetics of the Academy of Sciences of the Czech Republic. Martin is a postdoctoral fellow in the Laboratory of Biology of the Cell Nucleus led by Pavel Hozák. The CSHL first-timer is on campus for the 2018 Nuclear Organization & Function meeting where he presented a poster entitled “The functional characterization of PI(4,5)P2 - rich Nuclear Lipid Islets and their importance in regulation of RNA Polymerase II driven transcription”.

What are your research interests? What are you working on?
I am interested in understanding the relationship between nuclear architecture and regulation of RNA pol II transcription process. I employ a multi-disciplinary approaches using various imaging and biochemical techniques combined with the mass spectrometry to describe the role of phosphoinositides in nuclear compartmentalization. 

How did you decide to make this the focus of your research?
As I earned my PhD, I studied the involvement of actin cytoskeleton and phosphoinositide interactions in the regulation of bone homeostasis. During my first postdoctoral fellowship, I worked on protein-lipid interactions while studying the regulatory mechanisms of autophagy. Then six months ago, I had the great opportunity to join Professor Hozák’s laboratory which is pioneering in the field of nuclear phosphoinositides.    

How did your scientific journey begin? 
During my undergraduate studies, I became fascinated by how relatively small changes, like phosphorylation/dephosphorylation of a particular protein, can lead to a huge change in the entire cell behavior with drastic consequences, such as cancerous progression. I became interested in learning as much as I could about protein-protein interaction and their regulations, which led to my interest in protein-phospholipid interactions during my PhD and postdoctoral training. 

Was there something specific about Nuclear Organization & Function meeting that drew you to attend?
This meeting covers the main topic of my research which deals with nuclear compartmentalization, and it has fully met my expectations. 

What is your key takeaway from the meeting?
Realizing that the observations of other people are in accordance with a number of ours. 

What did you pick up or learn from the meeting that you plan to apply to your work?  
Biology of the cell nucleus in a very complex field wherein I still feel like a rookie. This meeting was a great opportunity for me to gain huge amounts of information from the field’s leading researchers, and to informally discuss and get feedback on my work. From this meeting and these discussion, I will return to my institute with several ideas for my research.  

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 highly recommend this meeting to a scientist at any stage of his/her career. I found it very helpful and inspiring, and think others will have the same experience.

How many CSHL meetings have you attended?
This is my first CSHL meeting, and I would be very happy if I get an opportunity to visit CSHL again in the future.

What do you like most about your time at CSHL?
I have to admit that in addition to the compelling scientific vibes, CSHL – Banbury where I was housed and the main area where the meeting was mostly held – is fantastically located. I am actually very sorry that I forgot to pack my running shoes because then I would have been able to see more of it. 

Martin’s participation at this meet was enabled by the Grant Agency of the Czech Republic (17-09103S) and the Institute of Molecular Genetics of the ASCR, v. v. i. institutional support (RVO: 68378050) . On behalf of Martin, thank you to these institutions for supporting and enabling our young scientists to attend CSHL meetings where they expand their knowledge and network. 

Thank you to Martin 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.