The pathophysiology of rare inherited gene mutations

Academic Medical Center (AMC)
September 08 2017
Position Type
Full Time
Organization Type

Our group studies how inherited DNA mutations lead to clinical disorders. In most of these cases the mutations we study occur only rarely, and in some cases have never before been reported in human disease. The spectrum of the clinical phenotypes we study is very wide and includes patients with metabolic disorders, brain abnormalities, dysmorphism and developmental defects, as well as bone marrow failure and cytopenia. In some of these cases we are also interested in the potential links of these mutations to developing cancer. In many of the genes we study we are focusing on how the mutations impair aspects of mitochondrial and cytoplasmic ribosome biogenesis, mRNA transport, and the translation of mRNA into protein.

This position will also focus on a project aimed at correcting single gene mutations in patients with a rare bone marrow failure disorder using CRISPR-Cas9. This translational aspect of the position will require working with inducible pluripotent stem cells (iPSCs).

The technician for this position will be responsible for developing assays in cellular models and primary patient cells for studying how the mutation or loss of different genes leads to specific cellular phenotypes. The techniques that will be used in these assays will include generating CRISPR-Cas9 knockout and immortalized cell lines, subcloning, qPCR, western blotting, next-generation RNA sequencing, polysome profiling, confocal microscopy, metabolic profiling, and others.

We have an extensive clinical network of patient samples and this position offers a unique and exciting opportunity to study the molecular mechanisms of undescribed gene mutations. Moreover, the translational aspect of the project will bring an opportunity to build the groundwork for developing future cures for these patients.

This job comes from a partnership with Science Magazine and Euraxess