Biochemistry & Proteomics Cell Biology Developmental Biology Gene Expression Genetics & Genomics Neurosciences
A 2023 Crick PhD project with Sila Ultanir
Project background and description
Neurons are highly specialized brain cells that receive input from thousands of synapses on their dendrites and relay output via their axon to numerous neurons. Development and maintenance of brain circuitry is essential for correct functioning and healthy ageing of the brain.
Ultanir lab studies kinase signaling cascades that are critical in neuronal development and function. Several kinases are genetically linked to neurological diseases in humans, yet their function in the brain are not known. A major focus in the lab is to reveal novel kinase substrates and kinase signaling mechanisms using a chemical genetic and global proteomics mass spectrometry methods [1-5]. The lab specializes in neurodevelopmental and neurodegenerative disease models in mice and human induced pluripotent stem cell (iPSC) derived neurons. To uncover the cellular functions of kinase – substrate signaling, Ultanir lab studies neuronal development, synaptogenesis and neurodegeneration using proteomics and transcriptomics approaches as well as cell biology methods (e.g. live imaging of microtubule based transport, autophagy analysis, immunostainings, histology, electrophysiology, shRNA mediated knockdowns, lentivirus and CRISPR-Cas9 mediated engineering). This PhD student project will aim to reveal kinase signaling defects in neurodegenerative diseases. The PhD student will receive training and will be expected to master methods on kinase biochemistry and use of mass spectrometry data and neuronal cultures, among others. They will gain extensive knowledge on cell biology of neurons, neuronal development and neurodegeneration using culture and in vivo models.
Candidates should have a good knowledge of biology, neuroscience, neurobiology or biochemistry. High motivation to work independently, ability to plan and organize their own time as well as be collaborative and help other team members when needed. Candidate should have experience in a laboratory environment.
1. Baltussen, L.L., Negraes, P.D., Silvestre, M., Claxton, S., Moeskops, M., Christodoulou, E., . . . Ultanir, S.K. (2018)
Chemical genetic identification of CDKL5 substrates reveals its role in neuronal microtubule dynamics.
EMBO Journal 37: e99763. PubMed abstract
2. Eder, N., Roncaroli, F., Dolmart, M.C., Horswell, S., Andreiuolo, F., Flynn, H., . . . Ultanir, S.K. (2020)
YAP1/TAZ drives ependymoma-like tumour formation in mice.
Nature Communications 11: 2380. PubMed abstract
3. Roşianu, F., Mihaylov, S.R., Eder, N., Martiniuc, A., Claxton, S., Flynn, H.R., . . . Ultanir, S.K. (2023)
Loss of NDR1/2 kinases impairs endomembrane trafficking and autophagy leading to neurodegeneration.
Life Science Alliance 6: e202201712. PubMed abstract
4. Baltussen, L.L., Rosianu, F. and Ultanir, S.K. (2018)
Kinases in synaptic development and neurological diseases.
Progress in Neuro-psychopharmacology & Biological Psychiatry 84: 343-352. PubMed abstract
5. Baskaran, P., Mihaylov, S.R., Vinsland, E., Shah, K., Granat, L., Ultanir, S.K., . . . Bateman, J.M. (2023)
Phosphorylation of the novel mTOR substrate Unkempt regulates cellular morphogenesis.
Journal of Biological Chemistry 299: 102788. PubMed abstract