Investigating how parental chromosomes organization shapes gene function

Jumana AlHaj Abed, PhD 
Postdoctoral Research Fellow
Department of Genetics
Harvard Medical School
Boston, MA, USA 

This conference is part of the the IRCM Early-Career Scientist Seminar Series (ECS3), a groundbreaking initiative whose mission is to showcase early career scientists. This is a great opportunity to discover the exciting projects of these researchers in training in front of a multidisciplinary audience.

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In person : 
IRCM Auditorium
110, avenue des Pins O, H2W 1R7 Montreal

Online :
Zoom link : https://zoom.us/j/95269762104
ID : 952 6976 2104
Code : 476372

IRCM conferences are set to occur under a hybrid format. However, please note that last-minute changes to online-only lectures may occur due to unforeseen circumstances. We invite you to visit this webpage again a few days before attending.

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About this conference : 
Somatic homolog pairing events are rare and transient in mammals, albeit critical and associated with processes such as DNA repair and X-inactivation. In contrast, Drosophila homologs are paired end-to-end in interphase somatic cells, and pairing-dependent gene regulation is detected at many loci, making it ideal for studying trans chromosomal interactions. To understand the structural and functional impact of trans homologous and heterologous interactions, I used complementary approaches at both the population and single-cell level. First, applying an allele-resolved Hi-C approach to Drosophila hybrid cells revealed a genome-wide, multilayer architecture of pairing and a variability in pairing precision. Excitingly, the more precise pairing correlated with high and low levels of gene expression, hinting at its potential regulatory role. Second, to test the consistency of these findings at the single-cell level, I imaged pairing at super-resolution using OligoSTORM, a single-molecule localization microscopy approach utilizing Oligopaint FISH probes and Homolog Specific Oligopaints. Imaging revealed that homologs intermingle extensively, and different types of pairing are packaged uniquely depending on their transcriptional state. These findings elucidating the allele-specific principles of genome organization, are a first step to addressing the trans structure-function relationship in specialized tissue and in other species.

About Jumana AlHaj Abed : 
Dr. Jumana AlHaj Abed graduated from Southern Methodist University (Dallas, TX) with a PhD in Molecular and Cell Biology and then joined the lab of Dr. Mitzi Kuroda at Harvard Medical School for a postdoctoral fellowship. She now pursues further postdoctoral training under the mentorship of Dr. Chao-Ting Wu. Her research aims to better understand the structure of homolog pairing, its functional consequences, and its relationship to epigenetic marks. Dr. AlHaj Abed has presented her work in several prestigious international conferences (Keystone Symposia, Gordon Research Conference, EMBO, Cold Spring Harbor Symposium, etc.). Her publication record includes, among several others, two papers in Nature Communications as first or co-first author.

Dr. AlHaj Abed will be joining the Max Planck Institute of Immunobiology and Epigenetics (Freiburg, Germany) in December 2023, as a Group Leader.

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Interview with Dr. Jumana AlHaj Abed

Question

Please tell us about your career path, leading up to your application to the Early-Career Scientist Seminar Series

Réponse | Answer 

“I studied Genetics at the Jordan University of Science and Technology in Jordan, and then was awarded a Fulbright scholarship to pursue my PhD. As a graduate student at Rick Jones lab at Southern Methodist University, I focused on understanding how epigenetic switches are established during early development. I found that the de novo recruitment of Polycomb group (PcG) proteins proceeds through an initial phase of surveying the chromatin environment before the stable binding of PcG proteins and the deposition and spreading of the repressive histone marks. Some of these transitions coincide with the increase in chromatin accessibility and emergence of genome organization. In fact, many gene regulatory programs could be affected by the surrounding chromatin and nuclear environment. For this reason, I moved on to Ting Wu’s lab at Harvard Medical School for my postdoc, to develop and utilize tools to better understand genome organization. I was especially interested in how the two sets of chromosomes we inherit from our parents communicate (i.e. parental chromosome interactions). During my postdoctoral training, I focused on next generation sequencing approaches and super-resolution imaging approaches to understand how often parental chromosomes interact, how close can parental chromosomes get and how that associates with gene function.”

Question
Please tell us about your passion for research. What motivates you most about your work? 

Réponse | Answer 

“I am excited to understand the interplay between epigenetic programs and how the parental genomes are packaged in the nucleus. How can we distinguish the purposeful genomic interactions that lead to specific outcomes from random movement in the nucleus? Recent research has shown that the way the genome is organized is non-random. In fact, it is multilayered and intricate, wherein chromosomes occupy unique territories, gene enhancers and promoters form dynamic loops, and chromatin active regions are more likely to interact with each other. Although we know some of the mechanisms governing gene regulation within a chromosome, less is known about the mechanisms governing interactions between maternal and paternal chromosomes. This is due to the difficulty in distinguishing parental chromosomes, since they are almost identical in sequence. Using allele-specific genomic approaches and advanced imaging technologies, I hope to better understand the mechanisms governing gene regulation between maternal and paternal chromosomes in the context of the nuclear environment.”

Question
Please tell us about your professional goals. What do you hope to accomplish as a scientist?

Réponse | Answer 

“I hope to continue to do research as an independent investigator, mentor graduate students and build a competitive international research program focused on i) understanding the structure and function of parental chromosomes, ii) revealing major players and events contributing to parental chromosome communication, iii) applying the allele-specific tools to investigate large chromosome abnormalities in disease and cancer.”