PhD student interested in improving diagnostics for patient with rare genetic disorders

Are you interested in the causes of rare genetic disorders and how to improve diagnostics for them? Would you like to work in a highly dynamic environment of the Sophia Children's Hospital and Erasmus MC, on the interphase of basic science and applied human clinical genetics, directly benefiting rare disease patients? And all of that in a fun, young and international team at a top university? Then join our expanding research team as our new PhD student!

The current position as PhD student in one of the research projects of the Rare Disease Center of Erasmus MC (location Sophia Children's hospital) is funded by a grant from the Erasmus MC Sophia Foundation. The project will focus on the diagnostics of patients affected by rare (genetic) disorders. Rare disorders, although individually rare, together affect 5-8% of the population as there are more than 8000 rare disorders. Symptoms of such disorders can include epilepsy, intellectual disability, but also immunodeficiency and cancer, they can affect all organs and they can be caused by genes involved in virtually any cellular process. For most there is no treatment yet, and they can lead to shortened lifespan and life long impact on well-being. It is often complicated to diagnose them, leaving patients and their families in longstanding insecurity and preventing optimal care (e.g. treatment and reproductive choices).

Genomic diagnostic technologies are a cornerstone in the diagnostics of rare disorders, as more than 70% of rare disorders are currently believed to be genetic. Despite advances, more than 50% of patients currently remain undiagnosed, indicating that further improvements in the diagnostic approaches are urgently needed. Our available technologies include SNP-arrays, whole exome (and since recently genome) sequencing, long-read sequencing, RNA-sequencing, DNA methylation analysis and metabolomics.

In this project, we aim to improve the diagnostics by determining the optimal diagnostic yield by testing combinations of technologies in a retrospective cohort study, followed by a prospective study in a rare disease cohort. From these comprehensive data we aim to generate a prediction model that aims to predict patient-specific optimal and fastest diagnostic routing. This will directly improve patient care at our Rare Disease Center and beyond.

As a PhD student, you are a highly motivated, creative, and communicative team player with strong problem-solving and coordination skills, along with a wide range of interests. You have a keen interest in state-of-the-art technologies, including short and long-read whole genome sequencing, whole exome sequencing, RNA-seq, metabolomics, and data integration. While an affinity for data analysis in these areas would be beneficial, it is not essential, as the project will primarily focus on the interpretation of the generated results rather than the primary analysis of sequencing data.

Specific job qualifications:

• Successfully obtained or soon to graduate with an MSc degree in Medicine, Health Science, Life Science, or a related field.
• Gained clinical experience and developed an interest in rare (genetic) disorders.
• Candidates with a medical background may be preferred due to the multidisciplinary nature of the project, which requires interpreting patient findings.
• Co-authorships on peer-reviewed publications relevant to this PhD topic are a strong plus, demonstrating your clinical experience in the rare disease field.
• Highly communicative with excellent verbal and written skills in both Dutch and English.
• Language skills must meet the minimum requirement (IELTS 7.0, TOEFL 100, or equivalent) to be considered.
• Willingness to share knowledge with other group members is essential.
• Preferably available to start immediately, or no later than September 30th, 2024.
• Ability to present a certificate of good conduct is required for appointment.

Your application should include:
Motivation letter, Curriculum Vitae, list of courses and obtained grades during BSc, and MSc program, a publication list, and a minimum of two supplied reference letters.

You will be part of a highly international working environment in an inspiring, dynamic and productive team at the Sophia Children's Hospital, Erasmus MC and the Rare Disease Center of the Erasmus MC. Look here for an introduction of our department.
Your primary affiliation will the Barakat and van Ham labs at the Clinical Genetics department, being embedded within the translational genomics, discovery and innovation teams of the department, working closely with diagnostics labs, and collaborating with the Erasmus MC departments of pediatrics, dermatology and metabolic disorders within the Sophia Children's Hospital.

Information about the department and research:
Background on the host labs and the Functional Genetics Unit

Publication records of the PIs including previous publications in Cell, Nature and Cell Stem Cell, can be found here and here.

Relevant publications related to this project include:
Dekker et al: "Web-accessible application for identifying pathogenic transcripts with RNA-seq: Increased sensitivity in diagnosis of neurodevelopmental disorders" Am J Hum Genet. 2023 Feb 2;110(2):251-272. doi: 10.1016/j.ajhg.2022.12.015
Douben et al: "High-yield identification of pathogenic NF1 variants by skin fibroblast transcriptome screening after apparently normal diagnostic DNA testing" Hum Mutat. 2022 Dec;43(12):2130-2140. doi: 10.1002/humu.24487
Deng et al: "A novel functional genomics atlas coupled with convolutional neural networks facilitates clinical interpretation of disease relevant variants in non-coding regulatory elements" medRxiv 2024 doi: https://doi.org/10.1101/2024.04.13.24305761
Yousefi et al: "Comprehensive multi-omics integration identifies differentially active enhancers during human brain development with clinical relevance". Genome Med. 2023, doi: 10.1186/s12073-021-00980-1
Deng et al: "AMFR dysfunction causes spastic paraplegia in human amenable to statin treatment in a preclinical model" Acta Neuropathologica, 2024 doi: 10.1007/s00401-023-02579-9

Examples of our previous work in the news:
Zebrafish and stem cells solve medical conundrum
Discoverers of very rare form of epilepsy now on track to treatment
Signposts for genetically unexplained brain disorders
Toch een diagnose dankzij RNA

If you are excited by the thought of this position and would like to apply, please do so by using the application form on our website.

For more information about this position, please contact Stefan Barakat, associated professor and principal investigator via t.barakat@erasmusmc.nl

No agencies please.