Different regions of the chromosome can be kept in either active or repressed states. The ability to control repression of such regions is central both to development, where information encoding for opposite cell types has to remain unavailable to ensure the stability of a lineage, and for the health of the genome, to silence foreign and repetitive genetic elements. The structure that confers this type of repression is termed heterochromatin. Our research interests reside in uncovering the mechanisms that underlie the assembly and fidelity of inheritance of heterochromatin, which is a specialized protein-nucleic acid composite. Unraveling these mechanisms is key to understanding the manner in which large stretches of the genome can be precisely and heritably partitioned into active and inactive regions. The heterochromatin system presents some unique and unusual features for a cellular self-assembly, such as nucleated, template-guided polymerization to a precise positional extent that have remained difficult to study. Addressing these features requires a multidisciplinary framework integrating biochemical and novel single cell genetic approaches.
How does heterochromatin spread? Heterochromatin is a specialized protein-nucleic acid composite that silences the activity of genes over large contiguous chromosomal regions, and that has been visualized as a distinct nuclear ultra-structure for almost a century. Remarkably, the mechanisms guiding heterochromatin spreading along the chromosome cycle remain obscure, even though it is this process that is central to patterning the genome during differentiation. We take biochemical, biophysical and genetic approaches to this question. Learn more...
How is it inherited? After a pattern of open and closed genomic regions is established in differentiation by the spreading reaction, this pattern has to be maintained through cell division for the cell to maintain its newly acquired fate. It is unclear how heterochromatin remains over a precisely delimited region across cells of a given cell type and how this positional memory is maintained through cell division cycles. We take single cell genetic and genomic approaches to tackle this question. Learn more...
Get involved! The Al-Sady lab is always looking to train mentees in the areas of single cell biology, chromatin biochemistry and biophysics. See if there is a project for you! We even train each other in a classroom setting, via our workshop program. Beyond just training in the lab, we are committed to bringing science education to the broader public via lab-specific outreach events, or as part of sponsored programs. Learn more...
The Al-Sady lab: Who we are and our mission.
The Al-Sady lab is an interdisciplinary lab interested in understanding how molecular machines work on chromosomes to assemble and maintain repressive epigenetic domains. Answering these questions requires a diverse team of researchers, from undergrads to postdocs, with different experiences, ways of thinking and backgrounds. We are passionate about training and brining science to the community. The Al-Sady lab welcomes trainees of any race, religion, national origin, gender identity, caregiver and family commitments, political affiliation, sexual orientation, and eligible age or ability. We believe Black Lives Matter and are committed to sustained action to reduce racism and inequity in science.
The Al-Sady Workshops
Trainees in the labs present a formal workshop on a topic of their choice. The objective of this workshop is to develop teaching skills around a student or postdoc's existing research (e.g., facilitated diffusion, machine learning). The trainee interactively presents their material, sometimes even involving board games! This archive is a resource of all trainees to and the wider community for teaching materials and the background in discussed topics. (Archive of all the prior workshops)
Teaching:
Partnership with USF: The Al-Sady lab is organizing an NSF funded teaching opportunity for UCSF graduate students and postdocs to teach one lecture of an elective course at the University of San Francisco (USF), focused on broad topics on epigenetics. In this opportunity, our trainees will learn how to deliver lectures to undergraduate students with feedback on pedagogy, helping them build a teaching portfolio.
Opportunities:
Please direct any queries to [email protected]
