Genomic medicine awards

Awarded to Louis Grandjean for £23,710 as part of the new projects call 2023.

In an infectious diseases outbreak it is important to identify the source case (where the outbreak came from) in order to implement appropriate treatment and preventive measures. This project will use high resolution whole genome DNA sequencing to improve identification of the source case in an infectious diseases outbreak. This new technology will help us to understand the origins of infectious diseases outbreaks and even potentially to identify superspreaders of infectious disease in the future. Identifying superspreaders (those individuals that give rise to many secondary cases) could allow us to target infection control interventions to have greater impact.

Awarded to Emil Gustavsson for £8,700 as part of the new projects call 2023.

Niemann-Pick Disease Type C (NPC) is a rare genetic condition that affects children. It arises due to changes in the NPC1 gene, leading to an accumulation of fatty substances inside the cells. This buildup results in complications in the brain, nerves, and other organs as time progresses. Unfortunately, there is no cure for NPC. The existing approaches focus on supportive therapies and targeted symptom management. However, there is hope for a new kind of treatment called antisense oligonucleotide (ASO) therapy, which can be used to target and reduce abnormal molecules produced because of changes in NPC1. Nevertheless, it is important to maintain normal gene function while reducing the abnormal molecules. Also, there might be other molecules produced due to these gene changes that we do not completely understand. Understanding these molecules can help make the therapy work better and avoid unexpected issues. Our project is all about filling in these gaps in knowledge.

To achieve this, we will use a state-of-the-art technique known as long-read sequencing. This advanced method allows us to thoroughly analyse all the molecules produced by the NPC1 gene. Our investigation will focus on cells obtained from a patient with NPC caused by NPC1 gene changes. Subsequently, we will subject these cells to a novel ASO treatment and compare them to normal cells. This approach will enable us to elucidate how genetic changes impact these molecules and identify those that the new treatment can rectify. Notably, this research extends beyond the realm of improving NPC treatments; it highlights the potential of long-read sequencing as a valuable tool for exploring other genetic conditions.

In conclusion, our study, which delves into the complete spectrum of molecules generated by the NPC1 gene, holds the promise of advancing NPC treatments. Furthermore, it underscores the broader applicability of this analysis technique in investigating a range of genetic diseases.

Awarded to Natalie Chandler for £25,000 as part of the new projects call 2023.

Our genome codes for what diseases we have as well as features such as eye and hair colour. Rare diseases occur in 1/17 people and can be very serious. These are caused by changes in our genomes. New treatments are being developed that can treat conditions with particular genomic changes, but in the past, it could take years and required many tests to identify the causal genetic change.

Whole genome sequencing (WGS) is a test that is now available in the NHS, and which looks for changes across nearly all of the genome in one go. However, the test currently used, called “short read” sequencing, still leaves gaps in sequencing meaning we may fail to find the cause of the condition. New technologies called “long-read” sequencing can examine these gaps and early studies have shown this can make a diagnosis in an extra 4% of patients.

We plan to compare the two WGS tests by using this new technology on a group of patients where current testing failed to find the cause of their condition, to see if this can increase the rate of diagnoses. If we find that it looks useful, we will also look at how difficult this is to do and how much it might cost, and other aspects needed to bring this from research to a clinical service for routine use. We will also look at whether it might replace the short read test or if the two should be used together.

Our team is based in the North Thames Genomics Laboratory Hub, and we work alongside the scientists doing the clinical service testing. This means we understand what is required to bring new tests into service and how to make this happen quickly if things look promising. In this project we will be testing patients with epilepsy and prenatal cases where we don’t have a diagnosis but where we know a quick diagnosis is vital. Developing these tests is costly and the companies who make these tests are helping by offering substantial discounts to do this work.

Awarded to Michelle Lowe for £2,000. Also under the PPIE theme.

Some Black and Asian women do not readily access maternity care and so may face worse maternal outcomes. Women from these groups are also often not included in research studies. This means that we know little about their experiences of maternity care – especially their feelings towards genetic testing during pregnancy. Better understanding the needs that might be unique to these communities could prevent racial inequalities in maternal care and improve outcomes. By working together with parents from these communities, this work will guide future research on maternity care, including a project looking at the experiences of Black and Asian parents who are offered genetic testing in pregnancy. In the study described here Black and Asian parents will be asked to join a discussion group where they will watch a video about prenatal sequencing (a genetic test offered in pregnancy) before sharing their views on this test with the group. They will also be asked for their views on a future research project, and their thoughts on what might encourage or put people off taking part in genetic research studies. Working together will make sure that the future project reflects the needs of these communities and sharing the results from these sessions will help researchers understand the issues that are important when planning studies with people from these backgrounds. Parents will also be sent a summary of the results and will be invited to an online event showcasing these results where they can see the role their input had in the research. Importantly, this work will help researchers build relationships with parents from Black and Asian communities and let them know about organisations like Antenatal Results and Choices (ARC) who support all parents making decisions about testing during pregnancy but who might be less well known to these groups.

1. Project: Application of Bioinformatics methods for clinical metagenomics to blood transfusion safety and an outbreak of unexplained acute hepatitis in children.

Awarded to Sarah Buddle for £2,693.

2. Project: Genomic differences in SARS-CoV-2 between children and elderly: implications for disease severity and transmission dynamics.

Awarded to Tereza Masonou for £3,302.

Also part of the Career Development Academy.

Project: The mosaic brain: a new diagnostic approach in focal epilepsies.

Awarded to Flavia Matos Santo for £96,669.

Also part of the Career Development Academy.

1. Project: How do ciliary genes contribute to the aetiology of congenital hypopituitarism and related disorders?

Awarded to Louise Gregory.

2. Project: Understanding cell-to-cell communication in the tumour microenvironment of arteriovenous malformation.

Awarded to Maanasa Polubothu.

Also part of the Career Development Academy.