Multiplex Assays of Variant Effects (MAVE) Operations

Cellular Operations

Our work enables Sanger scientists to study the effect of changing each individual letter in the DNA code of a disease gene in turn. The resulting maps of 'comprehensive variant effect' help to improve genetic diagnoses, understanding of disease and treatment. To deliver at the speed and scale needed to achieve this enormous task, we have developed (and continually refine) a robust Saturation Genome Editing (SGE) pipeline that applies cutting-edge informatic, molecular, cellular and sequencing techniques.

Creating comprehensive variant effect maps to power personalised medicine

Advances in human sequencing technologies now allows us to study people’s genomes at single–DNA base resolution, providing profound insights into how diseases are linked to single nucleotide variants (SNVs) and how these variants can predict disease progression. Yet a substantial fraction of the human genome remains functionally uncharacterised, with the positive, negative or neutral effects of many SNVs being unknown.

To lay the foundations for truly personalised medicine – diagnoses and treatments based on clinical genetics – it is essential that the biological consequences of these Variants of Uncertain Significance (VUS) are understood. Only then can researchers and clinicians accurately model disease and discover the most effective therapies.

By deploying, developing and refining a range of cutting-edge biological, genomic and sequencing techniques, the Multiplex Assays of Variant Effects (MAVE) Operations team seeks to generate comprehensive variant effect maps for SNVs across a broad set of clinically important disease genes.

Saturation Genome Editing (SGE) at scale

We are a core facility within the Sanger Institute’s Scientific Operations department who run, develop and deliver a robust pipeline based on Saturation Genome Editing (SGE). Our approach integrates specialised molecular biology, cellular assays, and informatic analyses to systematically assess the functional impact of SNVs using a loss-of-function framework.

To deliver at scale, we continually seek to push the boundaries of what is possible in high-throughput SGE by combining technical innovation with operational excellence. We achieve this by creating bespoke software and employing high-throughput automation in both molecular and cellular workflows.

We work in close collaboration with faculty research groups at the Wellcome Sanger Institute, including the Adams Group and the Hurles Group, and contribute directly to the Atlas of Variant Effects.

Our approach

We are a multidisciplinary team that combines the talents of research assistants, technical specialists, and scientific managers working across an end-to-end pipeline that spans multiple areas of the Institute’s scientific operations.

Working and learning in a cross-functional environment

Given the breadth and diversity of this pipeline, we operate in a highly cross-functional manner. Our team members benefit from comprehensive cross-training in, and experience of:

• molecular biology
• cellular assays
• sequencing technologies
• bioinformatic methodologies.

This approach both upskills our staff and builds resilience across the scientific pipeline.

Supporting collaborative working and career development

Working in partnership across our team and the Institute

We place strong emphasis on teamwork and shared responsibility in delivering scientific projects. To equip all our team members, we foster a supportive and collaborative environment that enables effective knowledge sharing and high-quality scientific working practices.

In parallel, we work closely with partner groups across the Institute’s Cellular Operations, Sequencing Operations, and Informatics and Digital Solutions to ensure seamless integration across our workflows.

Training the next generation of genomic scientists

We are keen to train and support the next development of the next generation of genomic scientists. For this reason, we provide a constructive and inclusive environment for all scientists joining our laboratories. We have built in comprehensive training across all our processes to enable our members to develop their individual skills and combine their talents in a cohesive, high-performing team.

We are part of the wider Wellcome Sanger Institute community, and we offer opportunities beyond pipeline work, including dedicated time to support career development through the Technicians Commitment and public engagement activities via Connecting Sciences.