molecular recognition of nucleic acids
The JARM Lab focuses on elucidating molecular mechanisms by which proteins and small molecules recognize specific sequences of DNA and RNA to decode genetic information. Our research interests lie at the interface of genomics, molecular biology and biophysics.
technology
COGNATE SITE IDENTIFICATION (CSI) by HT-SELEX
DNA BINDING specificity of cooperative transcription factor (TF) complexes
TFs rarely act alone and generally control gene expression by binding to enhancers as multi-protein complexes. The JARM Lab explores the recognition rules of DNA by multi-protein complexes using CSI-Seq, a next-generation DNA sequencing method to determine the DNA specificity of DNA binding molecules. The large DNA binding sites allowed by CSI-Seq are ideal to study multi-protein TF complexes.
genetic variation and disease
‘Big science’ projects have extensively catalogued human genetic variations, including >17,000 single nucleotide variants associated with diseases or quantitative traits. Hundreds of these are non-synonymous mutations in TFs, but the overwhelming majority occur in non-coding regulatory regions of the genome.
Research questions
i. What is the impact of non-synonymous mutations on TF binding specificity?
ii. How do non-coding disease-associated variants impact TF recognition?
iii. What are the effects of these variants on the transcriptome?
i. What is the impact of non-synonymous mutations on TF binding specificity?
ii. How do non-coding disease-associated variants impact TF recognition?
iii. What are the effects of these variants on the transcriptome?
RNA binding by transcription factors, why not?
We aim to develop methodology to pursue the following research questions:
i. Is RNA binding a general property of TFs?
ii. Which DNA-binding domains can recognize RNA?
iii. Is RNA binding by DBDs sequence or structure structure specific?
i. Is RNA binding a general property of TFs?
ii. Which DNA-binding domains can recognize RNA?
iii. Is RNA binding by DBDs sequence or structure structure specific?