Research overview:
How does the cell make and quality control multi-pass membrane proteins like transporters, receptors and ion channels that are essential for cellular physiology? Our lab combines mechanistic cell biology, (structural) biochemistry and protein engineering to dissect the pathways and molecular machines that mature roughly 5,000 human membrane proteins to a fully functional state. We are developing nanobody-based tools to acutely perturb such dynamic intracellular pathways directly at the protein level and assess immediate functional consequences to the nascent (membrane) proteome.
A related area of focus will be to generate highly specific reagents that can fine-tune the cellular stress responses that adjust cellular protein folding and degradation capacity. Such reagents have potential future therapeutic applications as they can be used to either correct or increase the dysregulation of protein homeostasis in neurodegeneration/ageing or cancer, respectively.
Major techniques in the lab include: mammalian cell culture, flow cytometry, FACS, CRISPR knock-outs/ knock-downs/knock-ins, genome-wide perturbation screens, phage & ribosome display, protein purification from mammalian and E. coli cells, in vitro translation and membrane insertion assays. Many of these techniques are highly sought-after in the biotech industry as well.
Tino is the first in his family to attend college (FirstGen) and this experience has shaped his approach to mentorship. The successful candidate will have access to close mentorship and will witness first-hand how to set up a new lab. The lab has fantastic resources and is surrounded by a world-class, collaborative scientific environment. Outside from the lab, life in the sunny Bay area offers spectacular culinary, cultural, and outdoor recreational opportunities.
The Pleiner lab will be an inclusive space that fosters learning & curiosity, promotes team work and values mentorship to drive an innovative research program that pushes the boundaries of molecular biology.
Relevant publications:
(*denotes equal contribution co-first- and † denotes co-corresponding authorship)
Stevens, T.A., Tomaleri, G.P., Hazu, M., Wei, S., Nguyen, V.N., DeKalb, C., Voorhees, R.M.† and Pleiner, T.† (2023) A nanobody-based strategy for rapid and scalable purification of native human protein complexes. Nature Protocols
Pleiner, T.*, Hazu, M.*, Pinton Tomaleri, G.*, Nguyen, V.N., Januszyk, K. and Voorhees, R.M. (2023) A selectivity filter in the ER membrane protein complex limits protein misinsertion at the ER. J Cell Biol 222 e202212007. (On the cover)
Pleiner, T., Hazu, M., Tomaleri, G.P., Januszyk, K., Oania, R.S., Sweredoski, M.J., Moradian, A., Guna, A. and Voorhees, R.M. (2021) WNK1 is an assembly factor for the human ER membrane protein complex. Mol Cell, 81, 2693-2704.e12.
Pleiner, T.*, Tomaleri, G.P.*, Januszyk, K.*, Inglis, A.J., Hazu, M. and Voorhees, R.M. (2020) Structural basis for membrane insertion by the human ER membrane protein complex. Science, 369, 433-436.
Pleiner, T.†, Bates, M.† and Görlich, D.† (2018) A toolbox of anti-mouse and anti-rabbit IgG secondary nanobodies. J Cell Biol, 217, 1143-1154.