Adaptation of a high resolution, high throughput assay of immunoglobulin repertoires for commercial and clinical applications
Lead Research Organisation:
Babraham Institute
Department Name: Chromatin and Gene Expression
Abstract
Our immune system makes millions of different antibodies to fight infection by cutting and pasting together large sets of antibody genes in many different combinations. It is currently not possible to measure them all and it would be extremely useful to be able to do so. First, immunodeficient patients who can't make antibodies could be diagnosed and treated quicker and more accurately. Second many companies are making mouse models that generate human antibodies as powerful therapies against specific infections. They need to know which antibodies are amplified in response to a particular infection. We have developed VDJ-seq, an assay that can identify several hundred thousand different mouse antibody sequences in a sample. We will adapt VDJ-seq to analyse immunodeficient human patient samples and mouse models producing human antibodies in a rapid, high-throughput, cost-effective way that aims to improve patient treatment and accelerate commercial discovery of therapeutic antibodies.
People |
ORCID iD |
| Anne Corcoran (Principal Investigator) |
Publications
Yang J
(2017)
Establishment of mouse expanded potential stem cells.
in Nature
Von Meyenn F
(2016)
Impairment of DNA Methylation Maintenance Is the Main Cause of Global Demethylation in Naive Embryonic Stem Cells.
in Molecular cell
Von Meyenn F
(2016)
Comparative Principles of DNA Methylation Reprogramming during Human and Mouse In Vitro Primordial Germ Cell Specification.
in Developmental cell
Ta VB
(2012)
Highly restricted usage of Ig H chain VH14 family gene segments in Slp65-deficient pre-B cell leukemia in mice.
in Journal of immunology (Baltimore, Md. : 1950)
Stubbs TM
(2017)
Multi-tissue DNA methylation age predictor in mouse.
in Genome biology
Peat JR
(2014)
Genome-wide bisulfite sequencing in zygotes identifies demethylation targets and maps the contribution of TET3 oxidation.
in Cell reports
Patalano S
(2015)
Molecular signatures of plastic phenotypes in two eusocial insect species with simple societies.
in Proceedings of the National Academy of Sciences of the United States of America
Patalano S
(2022)
Self-organization of plasticity and specialization in a primitively social insect.
in Cell systems
Parry A
(2021)
Active turnover of DNA methylation during cell fate decisions.
in Nature reviews. Genetics
| Description | We have developed a DNA-based next generation sequencing assay that can quantify which genes are used to make antibodies in mouse and human |
| Exploitation Route | We have used the assay to show that immunodeficient patients have large differences in the diversity of their antibody repertoires. this approach can be used to stratify patients for better diagnosis and treatment. |
| Sectors | Healthcare |
| Description | They have been used to better understand antibody repertoires in immunodeficient patients |
| First Year Of Impact | 2013 |
| Sector | Healthcare |
| Description | Babraham KEC TAG |
| Amount | £25,424 (GBP) |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 12/2013 |
| End | 05/2014 |
| Description | GCRF-IAA |
| Amount | £30,000 (GBP) |
| Funding ID | BB/GCRF-IAA/02 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 12/2016 |
| End | 03/2017 |
| Description | GCRF-IAA |
| Amount | £26,000 (GBP) |
| Funding ID | BB/GCRF-IAA/17/02 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 10/2017 |
| End | 02/2018 |
| Description | Addenbrookes |
| Organisation | Addenbrooke's Hospital |
| Country | United Kingdom |
| Sector | Hospitals |
| PI Contribution | High-throughput analysis of patient antibody repertoires |
| Collaborator Contribution | Provision of patient samples, supporting data and clinical expertise |
| Impact | None as yet |
| Start Year | 2012 |
| Title | METHOD OF IDENTIFYING VDJ RECOMBINATION PRODUCTS |
| Description | A high-throughput, high resolution DNA-based next generation sequencing assay to interrogate the sequences of VDJ recombined gene products resulting from antigen receptor recombination. Patent licence granted in USA and Europe in 2017. Licence application pending in Japan. Undertaking active marketing, no commercial licensee finalised as yet. |
| IP Reference | EP2820153 |
| Protection | Patent granted |
| Year Protection Granted | 2015 |
| Licensed | No |
| Impact | Collaborations with academic, clinical and commercial interests, resulting in 3 grant applications, one of which was successful |
| Title | VDJ-seq next generation sequencing assay |
| Description | Novel DNA-based next generation sequencing assay for analysis of immunoglobulin and T cell receptor repertoires. |
| Type Of Technology | New/Improved Technique/Technology |
| Year Produced | 2016 |
| Impact | Interest from companies for licensing; interest from academics in availing of the assay for their research. Pending publication in Nature Protocols. |
| Title | VDJ-seq pipeline - Babraham Linkon |
| Description | Pipeline to analyse antigene receptor repertoire outputs of VDJseq assay |
| Type Of Technology | Software |
| Year Produced | 2017 |
| Open Source License? | Yes |
| Impact | Publication in Nature Protocols 2018 |
| Description | Babraham Institute Annual Schools Day |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | As part of Annual Schools Day, 12 GCSE and A level students spent a day in our lab, doing a small project. Many asked questions about our research and careers in biology. Positive feedback relayed after the visit by teachers. The feedback afterwards from the students was that biological research was more interesting and scientists more normal than the students expected. |
| Year(s) Of Engagement Activity | 2010,2011,2013,2014,2015,2016,2017,2018,2019,2020 |
| Description | Primary School visits |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Type Of Presentation | Workshop Facilitator |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | Visits were made to a local school. 60 Year 4 to 6 primary school children attended presentations and hands-on practical related to our science. The teachers reported an increase in understanding and interest in biological research and what real scientists do. We are frequently requested to visit. |
| Year(s) Of Engagement Activity | 2010,2011,2012,2013,2014,2015,2016 |