Wellcome Sanger Institute

Parts Group

Function of human DNA and its variation

Our goal is to understand how genetic background influences outcome of mutations. To do so, we measure, model, and modulate cell state across healthy and disease-relevant human genetic diversity. In the lab, we develop tools for genetic perturbations, and  use genome engineering and synthetic biology to create cell lines for screening cellular traits. 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 human DNA functions in different contexts. To do so, we assay important aspects of cell state, create accurate and useful quantitative models of the readouts, and map the determinants of variation using genetic screens across a range of genetic or environmental backgrounds.

We are a combined computational and laboratory based research group. In the lab, we develop tools for genetic perturbations, and use synthetic biology and genome engineering to create cell lines that report on various aspects of cell state, from signaling pathway activity to cell cycle stage. We measure changes to reporter activities via growth competition, single cell RNA sequencing, as well as by fluorescence-based readouts. 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.

Core team

Photo of Dr Felicity Allen

Dr Felicity Allen

Postdoctoral Fellow

Photo of Dr Daniele Muraro

Dr Daniele Muraro

Computational Biologist - Staff Scientist

Photo of Luca Crepaldi

Luca Crepaldi

Staff Scientist

Previous team members

Photo of Kasia Tilgner

Kasia Tilgner

Visiting Scientist

Photo of Dr Michelle McRae

Dr Michelle McRae

Senior Research Assistant/Laboratory Manager

Photo of Danesh Moradigaravand

Danesh Moradigaravand

Senior Bioinformatician

Related groups

Partners

We work with the following groups

External

Cancer Dependency Map

The Cancer Dependency Map aims to find a targetable dependency in each cancer cell.

 

Publications

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