Parts Group

Understanding human DNA function by engineering

Our goal is to mechanistically understand impact of mutations in human DNA. To do so, we engineer DNA variation in cells, measure its impact to assay outputs, and quantitatively model the mechanism in between. In the lab, we develop tools for genetic perturbations, and use genome engineering and synthetic biology to create cell lines for randomization, screening, or evaluation. In the office, we develop probabilistic models as well as software tools to accurately and efficiently analyse the readouts.

Research

Our goal is to understand how function arises from human DNA, and mutations disrupt it. To do so, we combine genetic perturbation and genome engineering methods with assays of cell state, create accurate and useful quantitative models of the readouts, and disentangle causality by experimenting in multiple contexts.

We are a combined computational and laboratory based research group. In the lab, we adapt, develop, and apply tools for genetic perturbations genomic assays. We engineer the genomes using CRISPR/Cas, prime editing, and recombinase systems to strike the balance of randomization, control, and noise needed to answer our questions. We quantify cell state by growth competition, single cell RNA sequencing, and sorting. Computationally, we model the salient aspects of data generating processes to understand the underlying biology. We create generative models of large scale genetic screens and their outputs, and cast it in software.

Approach

The following four statements describe our approach:

1) We get things done. We start projects with clearly defined goals, and publish both positive and negative results of the ones that pass the pilot stage. We deliver to our collaborators.

2) We work on important problems. We pick projects based on how much they impact our understanding of human cells, characterize the variation of gene function across individuals, or influence how others work.

3) We succeed as a team. We have a diverse mix of backgrounds and skillsets, complementing each other with our strenghts.

4) We are excited about science. We read broadly, discuss latest developments, and keep up to date both with the depth of our field, and the entire breadth of genomics.