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.

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                            [post_excerpt] => We are undertaking research to develop, optimise and assess the performance of key enabling experimental and computational technologies that will underly&nbsp;<span title="... this large international effort.">...</span>
                            [post_status] => publish
                            [comment_status] => closed
                            [ping_status] => closed
                            [post_password] => 
                            [post_name] => human-cell-atlas-group
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                            [post_date] => 2018-10-18 15:05:35
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                            [post_content] => 
                            [post_title] => High throughput gene editing
                            [post_excerpt] => The High Throughput Gene Editing team helped to deliver the gene editing requirements of the Institute's faculty and research
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                            [comment_status] => closed
                            [ping_status] => closed
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                            [post_name] => high-throughput-gene-editing
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                            [post_date] => 2018-04-06 10:23:04
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                            [post_content] => 
                            [post_title] => Cancer Dependency Map Analytics
                            [post_excerpt] => We design algorithms and tools to identify all cancer vulnerabilities and genetic dependencies, paving the way to new therapies
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                            [post_name] => cancer-dependency-map-analytics
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                            [ID] => 202664
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                            [post_date] => 2015-06-30 15:01:47
                            [post_date_gmt] => 2015-06-30 15:01:47
                            [post_content] => 
                            [post_title] => Cellular Generation and Phenotyping
                            [post_excerpt] => The Cellular Generation and Phenotyping (CGaP) core facility provides central cell biology support to the Sanger Institute, functioning as a contract&nbsp;<span title="... research group in partnership with faculty groups to carry out multiple, distinct and often large-scale cell biology projects. Some examples of our work include finding the genes essential to cancer cell survival, and the causes of rare developmental disorders. We also contribute to the COVID-19 Genomics UK consortium.">...</span>
                            [post_status] => publish
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                            [post_name] => cellular-generation-and-phenotyping
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    [introduction] => 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.
    [links] => 
    [partners_introduction] => We work with the following groups
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                            [post_title] => Open Targets
                            [post_excerpt] => Open Targets is an innovative, public-private partnership that uses human genetics and genomics data at large scale for systematic drug target&nbsp;<span title="... identification and prioritisation.">...</span>
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                            [post_date] => 2016-09-13 10:56:14
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                            [post_content] => 
                            [post_title] => Human Genetics
                            [post_excerpt] => The Human Genetics Programme is driving a step-change in our understanding of genetic causes and biological mechanisms of disease susceptibility <span title="... and progression, focusing on developmental disorders and diseases of the blood and immune system. We integrate population-scale genetics, longitudinal clinical data, and large-scale genetic perturbation studies in cellular model systems. We aim to transform the clinical utility of human genetic variation.">...</span>
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    [programmes_introduction] => 
    [publications] => lp2-group lp2
    [research] => 
    [research_introduction] => 
    [secondary_title] => Function of human DNA and its variation
    [slideshow] => 
    [title] => Parts Group
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                    [content] => <p><u><strong>Research</strong></u></p>
<p><strong>Our goal is to understand how human DNA functions in different contexts</strong>. 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.</p>
<p><strong>We are a combined computational and laboratory based research group</strong>. 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.</p>
<p><u><strong>Approach</strong></u></p>
<p>The following four statements describe our approach:</p>
<p><strong>1) We get things done</strong>. 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.</p>
<p><strong>2) We work on important problems</strong>. 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.</p>
<p><strong>3) We succeed as a team.</strong> We have a diverse mix of backgrounds and skillsets, complementing each other with our strenghts.</p>
<p><strong>4) We are excited about science</strong>. We read broadly, discuss latest developments, and keep up to date both with the depth of our field, and the entire breadth of genomics.</p>
                )
        )
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                                    [post_content] => 
                                    [post_title] => Moradigaravand, Danesh
                                    [post_excerpt] => I am an evolutionary biologist and genomic data scientist, broadly interested in the epidemiology and population genomics of major pathogens, <span title="... particularly in the context of the dissemination and emergence of antimicrobial resistance. Furthermore, I developed mathematical and simulation frameworks to elucidate complex evolutionary dynamics of microbial populations during adaptation and the impact of recombination on adaptation.">...</span>
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                                    [post_title] => Tilgner, Kasia
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                                    [post_title] => McRae, Michelle
                                    [post_excerpt] => Michelle has the responsibility for setting up the new laboratory for Dr Leopold Parts. Initially, the laboratory will be focused <span title="... on performing lentiviral-based CRISPR/Cas9 genome-wide screens in human cell lines with subsequent image-based phenotyping of cellular traits. The aim of the research is to interrogate changes in cellular phenotype, particularly in relation to survival after drug treatment or in diverse genetic backgrounds.">...</span>
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                                    [post_modified] => 2017-10-31 14:51:19
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                                    [post_title] => Crepaldi, Luca
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                                    [post_name] => crepaldi-luca
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                                    [post_modified] => 2020-07-22 12:52:40
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                                    [post_title] => Allen, Felicity
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                                    [post_content] => 
                                    [post_title] => Muraro, Daniele
                                    [post_excerpt] => My role is to provide computational analyses of (Single Cell) RNA-Seq data sets from a diversity of studies for my experimental&nbsp;<span title="... team working on stem cell differentiation and genetic mechanisms controlling metabolic disorders.">...</span>
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    [ID] => 202846
    [page_url] => https://www.sanger.ac.uk/group/parts-group/
    [page_title] => Parts Group
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    [post_url] => https://www.sanger.ac.uk/group/parts-group/
    [post_title] => Parts Group
    [post_content] => 
    [post_status] => publish
    [created_at] => 2015-10-15 11:14:03
    [updated_at] => 2020-09-21 15:09:58
    [custom_credit] => Wellcome Sanger Institute
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                            [post_date] => 2015-10-15 11:14:03
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                            [post_content] => 
                            [post_title] => Yusa Group
                            [post_excerpt] => The Yusa laboratory focuses on the development of genome engineering technologies that allow us to perform unbiased genome-wide genetic screens <span title="... in mammalian cells.">...</span>
                            [post_status] => publish
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                            [post_name] => yusa-group
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                    [description] => We share many interests with Dr. Kosuke Yusa's group, and collaborate with them on internal projects.
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                            [post_date] => 2016-08-04 11:23:46
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                            [post_content] => 
                            [post_title] => Human Genetics Administration
                            [post_excerpt] => The Human Genetics Administration comprises a five strong team that provides comprehensive support for the smooth running of the Human Genetics&nbsp;<span title="... Programme">...</span>
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                            [post_date] => 2019-09-11 15:29:44
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                            [post_content] => 
                            [post_title] => Gene Editing
                            [post_excerpt] => In collaboration with our colleagues in Cellular Operations and Stem Cell Informatics, our work focuses on supporting and delivering the gene&nbsp;<span title="... editing requirements of the Institute's faculty and research programmes. Through the adoption and implementation of modern genome editing techniques, we tailor our technical experience to help answer biological questions. We optimise, develop and democratise the delivery of genome editing tools and platforms for the Institute&rsquo;s research programmes. For our collaborating partners we provide an agile, project focused, cost effective and efficient service as well as develop and provide biological resources, technical support and training for research groups and their staff.">...</span>
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                            [post_date] => 2019-03-05 14:30:05
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                            [post_content] => 
                            [post_title] => Gene Editing and Cellular Research and Development
                            [post_excerpt] => We develop novel genome editing techniques, cellular differentiation and cellular phenotyping systems, especially with respect to high-throughput investigation of gene and&nbsp;<span title="... non-coding regulatory element function.">...</span>
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                            [post_date] => 2018-01-26 10:39:14
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                            [post_content] => 
                            [post_title] => Cellular Genetics Informatics
                            [post_excerpt] => Our team provides efficient access to cutting-edge analysis methods, environments and pipelines for Cellular Genetics programme, which leads and is involved&nbsp;<span title="... in a number of world-class research initiatives.">...</span>
                            [post_status] => publish
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                            [post_date] => 2015-08-12 12:05:53
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                            [post_content] => 
                            [post_title] => Garnett Group
                            [post_excerpt] => The Translational Cancer Genomics team investigate how genetic alterations in cancer contribute to disease and impact on response to therapy.
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                            [ping_status] => closed
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                            [post_modified] => 2020-07-23 16:55:07
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                            [post_title] => Bayraktar Group
                            [post_excerpt] => We seek to explore the vast cellular diversity in the human brain using large-scale spatial transcriptomics, imaging and functional screens.
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                            [post_title] => Human Genetics Informatics (HGI)
                            [post_excerpt] => Human Genetics Informatics (HGI) supports the scientific aims of the Human Genetics programme by developing and operating computational analysis workflows, managing&nbsp;<span title="... shared storage, and providing bioinformatics software tools for the use of researchers across all Human Genetics faculty groups.">...</span>
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                            [post_title] => Billker Group
                            [post_excerpt] => At the Sanger Institute Oliver Billker's group used experimental genetics in rodent models to study the basic biology of malaria&nbsp;<span title="... parasites and their interactions with host and mosquito vectors">...</span>
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                    [description] => We help create models for high throughput genetic screens carried out in Dr. Billker's group.
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                            [post_title] => Human Cell Atlas Group
                            [post_excerpt] => We are undertaking research to develop, optimise and assess the performance of key enabling experimental and computational technologies that will underly&nbsp;<span title="... this large international effort.">...</span>
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                            [post_title] => High throughput gene editing
                            [post_excerpt] => The High Throughput Gene Editing team helped to deliver the gene editing requirements of the Institute's faculty and research
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                            [post_name] => high-throughput-gene-editing
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                            [post_title] => Cancer Dependency Map Analytics
                            [post_excerpt] => We design algorithms and tools to identify all cancer vulnerabilities and genetic dependencies, paving the way to new therapies
                            [post_status] => publish
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                            [post_name] => cancer-dependency-map-analytics
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                            [post_date] => 2015-06-30 15:01:47
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                            [post_content] => 
                            [post_title] => Cellular Generation and Phenotyping
                            [post_excerpt] => The Cellular Generation and Phenotyping (CGaP) core facility provides central cell biology support to the Sanger Institute, functioning as a contract&nbsp;<span title="... research group in partnership with faculty groups to carry out multiple, distinct and often large-scale cell biology projects. Some examples of our work include finding the genes essential to cancer cell survival, and the causes of rare developmental disorders. We also contribute to the COVID-19 Genomics UK consortium.">...</span>
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                            [post_name] => cellular-generation-and-phenotyping
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                            [post_modified] => 2020-09-24 15:35:34
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Core team

Photo of Luca Crepaldi

Luca Crepaldi

Staff Scientist

Photo of Dr Daniele Muraro

Dr Daniele Muraro

Computational Biologist - Staff Scientist

Photo of Dr Felicity Allen

Dr Felicity Allen

Postdoctoral Fellow

Previous team members

Photo of Kasia Tilgner

Kasia Tilgner

Visiting Scientist

Photo of Danesh Moradigaravand

Danesh Moradigaravand

Senior Bioinformatician

Photo of Dr Michelle McRae

Dr Michelle McRae

Senior Research Assistant/Laboratory Manager

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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