LMCB Group Leader, Wellcome Career Development Fellow
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Research synopsis
During development cells specialise in response to signalling cues. To accomplish this, they must turn on and off gene expression programs. Cis-regulatory elements control gene expression with exquisite spatial and temporal precision. We know that they are bound by transcription factors, but it is still not trivial to find them, and we are not able to predict their activity from sequence. The primary goal of our research is to understand how the non-coding genome regulates cell fate decisions during development. Our strategy to achieve this is to study the mechanistic principles of cis-regulatory elements in development. Long-term, our aim is to predict the functional outcomes of non-coding variation in development and disease. To bridge molecular mechanisms of cis regulation to developmental phenotypic consequences, we combine in vivo embryology with in vitro cellular models. Our model system is the developing spinal cord, where a small combination of signals directs the specification of neural progenitors and therefore which neurons they will make. We use a variety of novel genomics and computational methods, developing new approaches when needed. Our current projects include state-of-the art proteomics and microscopy approaches to address the mechanistic principles of how cis-regulatory elements control cell fate choice between neural progenitors.
Selected publications
Delás MJ, et al (2023). Developmental cell fate choice in neural tube progenitors employs two distinct cis-regulatory strategies. Developmental Cell. doi.org/10.1016/j.devcel.2022.11.016
Delás MJ and Briscoe J (2020). Repressive interactions in gene regulatory networks: When you have no other choice. Current Topics in Developmental Biology. doi.org/10.1016/bs.ctdb.2020.03.003
Blassberg R, et al (2022.) Sox2 levels regulate the chromatin occupancy of WNT mediators in epiblast progenitors responsible for vertebrate body formation. Nat Cell Biol 24, 633–644 (2022). doi.org/10.1038/s41556-022-00910-2
Delás MJ et al (2019). lncRNA Spehd Regulates Hematopoietic Stem and Progenitor Cells and Is Required for Multilineage Differentiation. Cell Reports, doi.org/10.1016/j.celrep.2019.03.080
Delás MJ et al (2017). lncRNA requirements for mouse acute myeloid leukemia and normal differentiation eLife 6:e25607. doi.org/10.7554/eLife.25607
Funders
Wellcome
Research themes
Transcriptional regulation
Signaling pathways
Development
Cellular decision making
Technology
Light microscopy
Super-resolution microscopy
High throughput screening
Bioinformatics
Genomics
Epigenetic profiling
Flow cytometry