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We are looking for a motivated master student who is willing to work on the following project starting September 2027 (Academic Year 2027/2028):

Chromosomal segregation errors are recurrent in various biological contexts. These copy number variations (CNVs) can generate genetic diversity within somatic tissues by producing mosaic cell populations. In some cases, however, they lead to known disorders. CNVs, ranging from kilobases to megabases, have been associated with developmental anomalies of the central nervous system as well as neurological phenotypes, including autism, schizophrenia, and bipolar disorder¹. Distinct developmental models have been used to analyze genomic regions potentially linked to these diagnoses^2,3. However, a large scale study investigating the molecular mechanisms that connect specific cell groups to molecular behaviors is still lacking. Currently, more than 40 scRNA-seq datasets related to brain development, from fetal brain samples to organoids,are available.    

In this fully in silico (dry lab) study, we will apply an existing reference-independent karyotyping framework across these public datasets to ask two connected questions. First, which molecular pathways are consistently dysregulated in cells carrying chromosomal imbalance, across different developmental models. Second, whether the degree of karyotype complexity within the same sample correlates with the magnitude of transcriptional and signaling disruption, including changes in cell to cell communication networks.   

This project offers hands-on experience in scRNA-seq analysis, including quality control, clustering, differential expression, pathway enrichment analysis, and cell-cell communication inference. Working entirely with existing public datasets, this project is well suited to a student interested in computational biology, neurodevelopment, or genomics, and offers direct exposure to a novel single-cell karyotyping method as it's being applied to real, disease-relevant questions.      

1. Lee CT, Freed WJ, Mash DC. CNVs in neurodevelopmental disorders. Oncotarget. 2015 Jul 30;6(21):18238-9. doi: 10.18632/oncotarget.4853. PMID: 26285833; PMCID: PMC4621882.  
2. Tao H, Wu J, Han Y, Zhang B, Zhai J. Genetic etiology and pregnancy outcomes of fetuses with central nervous system anomalies. Arch Gynecol Obstet. 2024 Jun;309(6):2567-2574. doi: 10.1007/s00404-023-07152-z. Epub 2023 Jul 21. PMID: 37477678; PMCID: PMC11147918.  
3. Kostic M, Raymond JJ, Freyre CAC, Henry B, Tumkaya T, Khlghatyan J, Dvornik J, Li J, Hsiao JS, Cheon SH, Chung J, Sun Y, Dolmetsch RE, Worringer KA, Ihry RJ. Patient Brain Organoids Identify a Link between the 16p11.2 Copy Number Variant and the RBFOX1 Gene. ACS Chem Neurosci. 2023 Nov 15;14(22):3993-4012. doi: 10.1021/acschemneuro.3c00442. Epub 2023 Oct 30. PMID: 37903506; PMCID: PMC10655044.