Our mission is to understand disease biology from a functional genomics standpoint that empower new modes of treatment for disease.
Work in the Cribbs lab focuses on developing novel single-cell technology and computational analysis frameworks to aid this goal. We work in a highly collaborative and supportive environment.
Single-cell Technology Development
The advent of single-cell technologies has led to a better understanding of the complexity and diversity of the tissue microenvironment.However, these approaches only allow for the measurement of the distal parts of a transcript following short-read sequencing. Therefore, splicing and sequence diversity information is lost for the majority of the transcript. The application of long-read Nanopore sequencing to droplet-based methods is challenging because of the low base-calling accuracy currently associated with Nanopore sequencing.
While long-read sequencing offers many advantages over short-read sequencing, it also suffers from a much higher error rate (3-10%). Since single-cell sequencing relies on precise calling of cell barcodes, long-read sequencing is currently impractical for single-cell sequencing. This project will develop methodology to construct oligonucleotide barcodes with novel amidites (the building blocks for synthetic oligonucleotides) that provide inherent error detection and/or correction.
Selected Publication: Philpott et al, Nature Biotechnology, 2021
Mapping Cells Within Tendon Tissue
As part of the Human Cell Atlas, The Tendon Seed Network will spatially define the transcriptome of extracellular matrix-rich tissues such as tendon across multiple anatomic and micro-anatomic sites. To enable this, the project will develop clinical, laboratory, bioinformatics, and mathematical modelling tools and platforms.
Selected Publication: Baldwin et al, Nature Rheumatology Reviews, 2021
Novel Therapeutic Targets in Multiple Myeloma
Multiple Myeloma (MM) is a bone marrow cancer that affects over 5,700 new patients a year in the UK. Current response rates to treatment are varied and there is a mean survival age of only 4-5 years, with a 10-year survival rate of only ~3%. A significant proportion of treatment failure is due to the emergence of multi-drug resistance.
In 2020 I was awarded an MRC Career Development Fellowship to apply multi-modal single-cell sequencing tools to understand the aetiology of MM and drug resistance. Ultimately, the main goal of my research is to better understand MM disease biology so we can develop new medicines to treat this incurable disease.
Selected Publication: Cottone et al, Cancer Research, 2020