Lacra Bintu is an Assistant Professor in the Bioengineering Department at Stanford. Her lab performs single-cell and high-throughput measurements of chromatin and gene regulation dynamics, and uses these data to develop predictive models and improve mammalian cell engineering.
Lacra started working on the theory of gene regulation as an undergraduate with Jané Kondev from Brandeis University and Rob Phillips from Caltech. As a Physics PhD student in the lab of Carlos Bustamante at U.C. Berkeley, she used single-molecule methods to tease apart the molecular mechanisms of transcription through nucleosomes. She transitioned to studying the dynamics of epigenetic regulation in live cells during her postdoctoral fellowship with Michael Elowitz at Caltech.
Honors & Awards
Maximizing Investigators' Research Award, NIH-NIGMS (2018-2023)
Career Award at the Scientific Interface, Burroughs Wellcome Fund (2015-2020)
Postdoctoral Fellowship, Jane Coffin Childs Memorial Fund for Medical Research (2011-2014)
Beckman Fellowship, California Institute of Technology (2011-2014)
Harold M. Weintraub Graduate Student Award, Fred Hutchinson Center (2011)
Outstanding Graduate Student Instructor Award, University of California, Berkeley (2006)
Doris Brewer Cohen Endowment Award for best senior thesis, Brandeis University (2005)
Wien International Scholarship, Brandeis University (2001-2005)
Postdoctoral Fellow, California Institute of Technology, Biology and Biological Engineering (2016)
Ph.D., University of California, Berkeley, Physics (2010)
B.S., Brandeis University, Physics, Mathematics, Neuroscience (2005)
- Molecular and Cellular Bioengineering
BIOE 300A (Win)
Independent Studies (6)
- Bioengineering Problems and Experimental Investigation
BIOE 191 (Aut, Win, Spr, Sum)
- Directed Investigation
BIOE 392 (Aut, Win, Spr, Sum)
- Directed Study
BIOE 391 (Spr)
- Graduate Research
BIOPHYS 300 (Aut, Win, Spr, Sum)
- Out-of-Department Graduate Research
BIO 300X (Aut, Win, Spr, Sum)
- Practical Training
BIOE 299B (Sum)
- Bioengineering Problems and Experimental Investigation
- Prior Year Courses
Doctoral Dissertation Reader (AC)
Travis Ahn-Horst, Stevan Jeknic, Margarita Khariton, Thomas Lozanoski, Sedona Murphy, Artem Trotsyuk
Postdoctoral Faculty Sponsor
Taihei Fujimori, Jun Wan
Doctoral Dissertation Advisor (AC)
Michaela Hinks, Sarah Lensch, Connor Ludwig, Adi Mukund, Joydeb Sinha, Mike Van
Doctoral Dissertation Co-Advisor (AC)
Nicole DelRosso, Peter Suzuki, Josh Tycko
Master's Program Advisor
Janelle Kaneda, Ziv Lautman, Chuyi Wang
Beatriz Atsavapranee, Aris Kare, Yuxi Ke, Connor Ludwig, Kasra Naftchi-Ardebili, Taylor Nguyen, Marija Pavlovic, Mike Van
Nanobody-mediated control of gene expression and epigenetic memory.
2021; 12 (1): 537
Targeting chromatin regulators to specific genomic locations for gene control is emerging as a powerful method in basic research and synthetic biology. However, many chromatin regulators are large, making them difficult to deliver and combine in mammalian cells. Here, we develop a strategy for gene control using small nanobodies that bind and recruit endogenous chromatin regulators to a gene. We show that an antiGFP nanobody can be used to simultaneously visualize GFP-tagged chromatin regulators and control gene expression, and that nanobodies against HP1 and DNMT1 can silence a reporter gene. Moreover, combining nanobodies together or with other regulators, such as DNMT3A or KRAB, can enhance silencing speed and epigenetic memory. Finally, we use the slow silencing speed and high memory of antiDNMT1 to build a signal duration timer and recorder. These results set the basis for using nanobodies against chromatin regulators for controlling gene expression and epigenetic memory.
View details for DOI 10.1038/s41467-020-20757-1
View details for PubMedID 33483487
High-Throughput Discovery and Characterization of Human Transcriptional Effectors.
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 to a reporter, and their transcriptional effects are measured by sequencing. Using this approach, we measure gene silencing and activation for thousands of domains. We find a relationship between repressor function and evolutionary age for the KRAB domains, discover that Homeodomain repressor strength is collinear with Hox genetic organization, and identify activities for several domains of unknown function. Deep mutational scanning of the CRISPRi KRAB maps the co-repressor binding surface and identifies substitutions that improve stability/silencing. By tiling 238 proteins, we find repressors as short as ten amino acids. Finally, we report new activator domains, including a divergent KRAB. These results provide a resource of 600 human proteins containing effectors and demonstrate a scalable strategy for assigning functions to protein domains.
View details for DOI 10.1016/j.cell.2020.11.024
View details for PubMedID 33326746
Mapping chromatin modifications at the single cell level.
Development (Cambridge, England)
2019; 146 (12)
Understanding chromatin regulation holds enormous promise for controlling gene regulation, predicting cellular identity, and developing diagnostics and cellular therapies. However, the dynamic nature of chromatin, together with cell-to-cell heterogeneity in its structure, limits our ability to extract its governing principles. Single cell mapping of chromatin modifications, in conjunction with expression measurements, could help overcome these limitations. Here, we review recent advances in single cell-based measurements of chromatin modifications, including optimization to reduce DNA loss, improved DNA sequencing, barcoding, and antibody engineering. We also highlight several applications of these techniques that have provided insights into cell-type classification, mapping modification co-occurrence and heterogeneity, and monitoring chromatin dynamics.
View details for DOI 10.1242/dev.170217
View details for PubMedID 31249006
Mitigation of off-target toxicity in CRISPR-Cas9 screens for essential non-coding elements.
2019; 10 (1): 4063
Pooled CRISPR-Cas9 screens are a powerful method for functionally characterizing regulatory elements in the non-coding genome, but off-target effects in these experiments have not been systematically evaluated. Here, we investigate Cas9, dCas9, and CRISPRi/a off-target activity in screens for essential regulatory elements. The sgRNAs with the largest effects in genome-scale screens for essential CTCF loop anchors in K562 cells were not single guide RNAs (sgRNAs) that disrupted gene expression near the on-target CTCF anchor. Rather, these sgRNAs had high off-target activity that, while only weakly correlated with absolute off-target site number, could be predicted by the recently developed GuideScan specificity score. Screens conducted in parallel with CRISPRi/a, which do not induce double-stranded DNA breaks, revealed that a distinct set of off-targets also cause strong confounding fitness effects with these epigenome-editing tools. Promisingly, filtering of CRISPRi libraries using GuideScan specificity scores removed these confounded sgRNAs and enabled identification of essential regulatory elements.
View details for DOI 10.1038/s41467-019-11955-7
View details for PubMedID 31492858
Advancing towards a global mammalian gene regulation model through single-cell analysis and synthetic biology
Current Opinion in Biomedical Engineering
2017; 4: 174-193
View details for DOI 10.1016/j.cobme.2017.10.011