Undergraduate projects 2026–27
Combining genomic medicine and chronobiology
Dr Tim Hearn, Chronomic Medicine Group
Department of Genomic Medicine, University of Cambridge
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What is genomic medicine?
Using a patient’s whole genome sequence to find the cause of their disease
- 2018The NHS Genomic Medicine Service launched. The NHS was the first national health system to offer whole genome sequencing as part of routine care.
- 100,000genomes were sequenced from about 85,000 NHS patients with rare disease or cancer for the 100,000 Genomes Project.
- 1 in 17people will have a rare disease at some point in their life, and around 80% of rare diseases have a genetic cause.
The human genome: 3.1 billion letters of DNA across chromosomes 1–22, X and Y
Zooming in on one chromosome
Then on one gene, made up of exons and introns
Then on a single letter of its DNA that has changed: a variant
- Computational project
- 1 student
- Genomics England data
Solve a rare disease patient!
Only 30% of cases from the NHS Genomic Medicine Service are currently solved. You will look for the causal variants in unsolved patients’ genomes and feed your findings back to the NHS.
With Tim Hearn and Bethan Lloyd-Owen
- 4–5 million differences from the reference genome
- About 10,000 change a protein
- A few hundred are rare in the population
- A handful are in genes linked to the patient’s symptoms
- One is the cause
Approximate numbers for one person’s genome
Solve a rare disease patient!
- Computational project
- 1 student
- Dry lab
- Addenbrooke’s Treatment Centre
The NHS genomic medicine service is here! Patients with rare diseases are now offered the opportunity to have whole genome sequencing performed on the NHS to identify a causal variant if standard testing fails. Only 30% of cases from the NHS genomic medicine service are currently solved. We need researchers to help us solve the many individuals who have been sequenced.
You will work in the Linux computing environment to examine potential causal variants in a set of patients, and feed your findings back to the NHS. This project has the potential to lead directly to improvements in a patient’s life.
Practical details
- The work uses the Genomics England 100,000 Genomes Project data, inside the secure Genomics England Research Environment.
- You will sign up to the Genomics England clinical interpretation partnership agreement and complete information governance training.
Contacts
Tim Hearn (tjh70@cam.ac.uk) and Bethan Lloyd-Owen
Reading
- 100,000 Genomes Pilot on rare-disease diagnosis in health care: preliminary report
- Standards and guidelines for the interpretation of sequence variants
- Efficient reinterpretation of rare disease cases using Exomiser
- Genome sequencing for diagnosing rare diseases
From our group
Where the funnel numbers come from
Chronomic medicine
Your DNA doesn’t change over the day, but your gene activity does
52% of disease-causing genes are predicted to oscillate across the day. We call the application of chronobiology to genomic medicine chronomic medicine.
- SeverityThe clock may help explain why the same variant is mild in one person and severe in another.
- DiagnosisVariants in the DNA that controls when genes are switched on could be missed causes of disease.
- TreatmentThe time of day a medicine is taken can change how well it works.
Drag the hand to change the time. Each bar is a gene that peaks at a different time of day. Times are typical for someone who sleeps at night.
Sources for this screen
The 52% figure is our group’s estimate of disease-causing genes predicted to oscillate across the day. Times on the dial are typical of a day-active adult and vary from person to person: core body temperature is lowest a couple of hours before waking, cortisol peaks shortly after waking, heart attacks are most common between 6 am and noon, and melatonin starts to rise two to three hours before bedtime.
- Computational project
- 1 student
- Genomics England data
Is circadian disruption of rhythmically expressed genes behind missing heritability in rare disease?
The same disease variant can be severe in one person and mild in another. You will test whether genetic variants that make people morning or evening types help to explain the difference.
With Tim Hearn and Millie Ampiah
Chronotype, whether you are a morning or an evening type, is partly genetic.
Missing heritability: what explains the difference between these two patients?
The project starts with endocrine disorders, where the disease genes are highly differentially expressed.
Is circadian disruption of rhythmically expressed genes behind missing heritability in rare disease?
- Computational project
- 1 student
- Dry lab
- Addenbrooke’s Treatment Centre
You will continue an existing study looking for associations between variants influencing genetic chronotype, the genetic basis for “morning” and “evening” people, and rare disease phenotype severity. We have previously identified loci that affect the severity of cardiac arrhythmias and you will continue this work with other candidate diseases.
There are many common endocrine disorders where the genetic aetiology is complicated and there is contribution from a variety of genes in related pathways to the overall disease phenotype. Endocrine disorders are excellent candidates for chronomic medicine, as the disease genes are highly differentially expressed. You will ascertain the number of genes on the endocrine disorders gene panel which are rhythmically expressed in patient samples. You will then perform an analysis on the patient genomes in the 100,000 Genomes Project endocrine disorders group.
It is possible to conduct this project on any other rare disease or cancer of interest to a student.
Practical details
- The work uses the Genomics England 100,000 Genomes Project data, inside the secure Genomics England Research Environment.
- You will sign up to the Genomics England clinical interpretation partnership agreement and complete information governance training.
Contacts
Tim Hearn (tjh70@cam.ac.uk) and Millie Ampiah
Reading
- Towards chronomic medicine: enrichment and linkage of chronotype markers with rare disease associated genes
- Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms
- A database of tissue-specific rhythmically expressed human genes has potential applications in circadian medicine
- Polygenic background modifies penetrance of monogenic variants for tier 1 genomic conditions
From our group
- Human phenotype ontology clustering may uncover potential congenital adrenal hyperplasia cases in the 100 000 Genomes Project
- Enrichment of CYP21A2 promoter variant rs150223621 in congenital adrenal hyperplasia cohorts from the 100 000 Genomes Project
- A candidate genetic modifier and autosomal recessive cause of Brugada syndrome that may alter the circadian expression of SCN5A
- Lab project
- Human cell culture
Timing of human cell clock
Almost every cell in the body has its own circadian clock. You will synchronise cultured human cells with a brief hormone pulse and measure when the clock genes are expressed across the day.
With Tim Hearn
Out of step, the cells’ rhythms cancel each other out.
Timing of human cell clock
- Lab project
- Human cell culture
Our body clock runs inside individual cells, where clock-gene expression rises and falls at characteristic times of the day. A brief hormonal pulse can synchronize cultured cells so that their clocks run in phase, allowing us to study these rhythms under controlled experimental conditions.
This project will characterize clock-gene activities in human cells across the day, using a range of experimental techniques, to better understand the biology of circadian rhythms.
Contact
Tim Hearn (tjh70@cam.ac.uk)
Reading
- Computational project
- Software and benchmarking
Developing and benchmarking Native Workbench: accessible, reproducible bioinformatics on Windows
Native Workbench is a Windows desktop application that runs established bioinformatics tools and records how each result was produced. You will develop it further and compare it with the same analyses run on Linux.
With Tim Hearn. Experience of AI agents and GitHub would be an advantage.
- Correctness
- Performance
- Usability
- Reproducibility
Developing and benchmarking Native Workbench: accessible, reproducible bioinformatics on Windows
- Computational project
- Software and benchmarking
Running bioinformatics analyses can involve complex software setup, creating barriers for students and researchers. Native Workbench is a Windows desktop application designed to make established analysis tools easier to run locally while recording how results were produced.
This project will develop the application further and evaluate its scientific correctness, performance, usability and reproducibility. The student will test workflows such as sequence quality control, alignment and variant calling using datasets with known expected results and larger, realistic datasets. Scientific outputs, execution times and computing-resource use will be compared with equivalent Linux analyses under matched conditions wherever practical.
Testing across different Windows computers and structured user feedback will guide improvements to installation, workflow construction and error recovery. The project will deliver an improved application and a reproducible benchmark suite, alongside evidence-based guidance on its capabilities and limitations.
Practical details
- A good understanding of the use of AI agents and GitHub would be an advantage.
Contact
Tim Hearn (tjh70@cam.ac.uk)
Reading
Dissertation topics
The relevance of circadian clocks to cardiovascular disease
What do we know about circadian clocks in Daphnia, a potential model crustacean?
Is bioinformatics a data science?
- Dissertation
Reading list
- What is bioinformatics? A proposed definition and overview of the field
- 50 years of data science
- Is “bioinformatics” dead?
Contact
Tim Hearn (tjh70@cam.ac.uk)
The relevance of circadian clocks to cardiovascular disease
- Dissertation
Starting points
From our group
- Daily rhythms in heartbeat rate are intrinsic to the zebrafish heart
- A systematic review of utilisation of diurnal timing information in clinical trial design for Long QT syndrome
Contact
Tim Hearn (tjh70@cam.ac.uk)
What do we know about circadian clocks in Daphnia, a potential model crustacean?
- Dissertation
From our group
Starting points
- Genome-wide profiling of 24 hr diel rhythmicity in the water flea, Daphnia pulex: network analysis reveals rhythmic gene expression and enhances functional gene annotation
- Daphnia as a versatile model system in ecology and evolution
- The ecoresponsive genome of Daphnia pulex
Contact
Tim Hearn (tjh70@cam.ac.uk)
Come and talk to us
Get in touch about any of the projects or dissertations, or to visit the lab.
Dr Tim Hearn
tjh70@cam.ac.uk
Level 6, Addenbrooke’s Treatment Centre, Cambridge Biomedical Campus