Combining genetic tools like induced protein degradation with single-cell imaging (described above) we aim to improve our understanding of the molecular mechanisms that shape genome function. Schematic
Correct patterning and development of many mammalian tissues depends on the activity on cis-regulatory interactions at ultra-long range. We are interested to understand how such long range regulatory interactions are established, and how they derive specificity. Several examples we are studying in the lab include distal enhancers for Pitx1 expression in posterior limbs (300 kb), distal enhancers of Myc (700 […]
We are interested to learn to what extent changes in 3D genome folding facilitate changes in cell fate during development, using both fly and mouse development as a model system. In Drosophila, distinct levels of 3 posterior Hox genes specify the anterior-posterior cell identities in the 10 most posterior segments of the animal. The three genes are positioned next to […]
We are interested in developing microscopy tools for single cell genomics and transcriptomics and applying these to understand transcriptional regulation during development.
Mathematical models allow us to develop rich predictions from quantitative measurement. This approach to date has been vastly more successful in physics than molecular biology, where models have enable us to predict the existence of fundamental particles long before they are detected in nature, or determine the mass of celestial bodies that we could never put on a scale and […]
Single molecule fluorescent in situ hybridization (FISH) is a powerful technique to label and count individual RNA molecules of a particular type inside a fixed cell or tissue. It allows us to study the organization of RNAs within a cell and the organization of cell-types (classified by RNA expression) within a complex tissue or environment. The ability to have precise […]
In order to study the 3D DNA structures which regulate contacts between cis-regulatory elements (CREs) and their target transcribed elements (TEs), we are developing a super-resolution imaging approaches capable of resolving tens to hundreds of individual CREs, TEs, and intervening sequence in single cells of sectioned embryonic tissue and cultured cells at better than 20 nm resolution. We are applying this approach […]
Differences in gene expression arise due to differences in how accessible the sequence encoding a gene is to the transcription machinery of the cell. While we know much about the structure of DNA at small lengths scales (<1 kilobase) and at large length scales (whole chromosomes), we understand little about its organization at the intermediate scale of kilobases to megabases. […]