A5021907794- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Protein Degradation and Inhibitors
- Viral Infectious Diseases and Gene Expression in Insects
- Protein Structure and Dynamics
- Ubiquitin and proteasome pathways
- Gene Regulatory Network Analysis
- Computational Drug Discovery Methods
- Gene expression and cancer classification
- Genomics and Phylogenetic Studies
- Estrogen and related hormone effects
- Healthcare Policy and Management
- RNA Interference and Gene Delivery
- Health Systems, Economic Evaluations, Quality of Life
- Insect Resistance and Genetics
- Bacterial Genetics and Biotechnology
- RNA Research and Splicing
- LGBTQ Health, Identity, and Policy
- Healthcare cost, quality, practices
- Machine Learning in Bioinformatics
Stanford University
2020-2024
Palo Alto University
2024
Duke University
2018
We present osprey 3.0, a new and greatly improved release of the protein design software. Osprey 3.0 features convenient Python interface, which improves its ease use. It is over two orders magnitude faster than previous versions when running same algorithms on hardware. Moreover, includes several algorithms, introduce substantial speedups as well biophysical modeling. also GPU support, provides an additional speedup order magnitude. Like , offers unique package advantages other software,...
Abstract Human nuclear proteins contain >1000 transcriptional effector domains that can activate or repress transcription of target genes. We lack a systematic understanding which regulate robustly across genomic, cell-type, and DNA-binding domain (DBD) contexts. Here, we developed dCas9-mediated high-throughput recruitment (HT-recruit), pooled screening method for quantifying function at endogenous targets, tested library containing 5092 protein Pfam varied find many effectors depend on...
In mammalian cells genes that are in close proximity can be transcriptionally coupled: silencing or activating one gene affect its neighbors. Understanding these dynamics is important for natural processes, such as heterochromatin spreading during development and aging, when designing synthetic regulation circuits. Here, we systematically dissect this process single by recruiting releasing repressive chromatin regulators at dual-gene reporters, measuring how fast reactivation spread a...
Summary Human gene expression is regulated by over two thousand transcription factors and chromatin regulators 1,2 . Effector domains within these proteins can activate or repress transcription. However, for many of we do not know what type transcriptional effector they contain, their location in the protein, activation repression strengths, amino acids that are necessary functions. Here, systematically measure activity >100,000 protein fragments (each 80 long) tiling across most human...
The data that support the findings of this study are available on request from corresponding author. not publicly due to privacy or ethical restrictions.
Abstract Despite growing knowledge of the functions individual human transcriptional effector domains, much less is understood about how multiple domains within same protein combine to regulate gene expression. Here, we measure activity for 8,400 domain combinations by recruiting them reporter genes in cells. In our assay, weak and moderate activation synergize drive strong expression, while combining activators often results weaker activation. contrast, repressors linearly produce full...
We present OSPREY 3.0, a new and greatly improved release of the protein design software. 3.0 features convenient Python interface, which improves its ease use. It is over two orders magnitude faster than previous versions when running same algorithms on hardware. Moreover, includes several algorithms, introduce substantial speedups as well biophysical modeling. also GPU support, provides an additional speedup order magnitude. Like OSPREY, offers unique package advantages other software,...
Summary Thousands of proteins localize to the nucleus; however, it remains unclear which contain transcriptional effectors. Here, we develop HT-recruit - a pooled assay where protein libraries are recruited reporter, and their effects measured by sequencing. Using this approach, measure gene silencing activation for thousands domains. We find relationship between repressor function evolutionary age KRAB domains, discover Homeodomain strength is collinear with Hox genetic organization,...
Abstract In mammalian cells genes that are in close proximity coupled transcriptionally: silencing or activating one gene can affect its neighbors. Understanding these dynamics is important for natural processes, such as heterochromatin spreading during development and aging, when designing synthetic regulation. Here, we systematically dissect this process single by recruiting releasing repressive chromatin regulators at dual-gene reporters, measuring how fast reactivation spread a function...