Assistant Professor in Residence of Genetics, Genomics, Evolution, and Development

Full Directory Information

Research Interests

Transcriptional regulation is essential for development, stress responses and homeostasis. The transcription factors that activate transcription contain DNA binding domains and activation domains. DNA binding domains are conserved and structured, and can be predicted from amino acid sequence. On the other hand, activation domains are poorly conserved and intrinsically disordered: they do not fold into a single structure and instead inhabit many conformations. As a result, it has been difficult to study activation domains and to predict them from amino acid sequence.

In my group, we use high-throughput experiments, machine learning, evolutionary comparisons, and all-atom simulations to study the protein sequence properties that contribute to activation domain function. We design complex mutations to test mechanistic hypotheses for protein function and test 100-1000s of mutations in yeast and human cells. We seek the design principles for how activation domains work, how they bind partners, how they evolve, and how we can predict them from protein sequence.

Current Projects

• ​Investigating the sequence features of different classes of transcriptional activation domains
• Predicting different types of activation domains from protein sequence
• Probing transcription factor evolution
• Characterizing Variants of Uncertain Significance in activation domains of ASD-associated transcription factors

Selected Publications

SR Kotha and MV Staller. 2023 The balance of acidic and hydrophobic residues predicts acidic transcriptional activation domains from protein sequence. Genetics, iyad131, https://doi.org/10.1093/genetics/iyad131

MV Staller. 2022. Transcription factors perform a two-step search of the nucleus. Genetics. October 2022. 222(2), https://doi.org/10.1093/genetics/iyac111. Featured article.

MV Staller, E Ramirez, SR Kotha, AS Holehouse, RV Pappu, BA Cohen. Directed mutational scanning reveals a balance between acidic and hydrophobic residues in strong human activation domains. 2022. Cell Systems. 13, 334-345.e5 https://doi.org/10.1016/j.cels.2022.01.002

MV Staller, AS Holehouse, D Swain-Lenz, R Das, RV Pappu, BA Cohen. A High-Throughput Mutational Scan of an Intrinsically Disordered Acidic Transcriptional Activation Domain. Cell Systems. 2018 6(4):444-455.

Last Updated 2023-07-27