A PhD student position is available in the Freund group at FU Berlin (https://www.bcp.fu-berlin.de/en/chemie/biochemie/research-groups/freund-group/index.html) for 4 years in the project “The role of the palmitoylation switch in activated T cells”. Lipid-modification of proteins with palmitate is catalyzed by cellular palmitoyl transferases. These so-called DHHC enzymes steer the transport, membrane compartmentation and function of hundreds of proteins and are involved in the immune cell function of T cells. Furthermore, many potentially zoonotic viruses require palmitoylation by DHHC enzymes for infectivity. We have previously profiled the T cell palmitome and unraveled the role of individual palmitoylation events for T cell function (https://www.nature.com/articles/srep11598). In addition, affinity purification-mass spectrometry was used to define the interaction between DHHC20 and T cell proteins. Subsequently direct binding between DHHC20 and a trimeric G protein was shown to mediated by the beta-gamma subunit of the latter (https://www.biorxiv.org/content/10.1101/2024.02.14.580290v1). Currently we are investigating the DHHC/target interplay in the context of T cell signaling and viral interference, with the goal to mechanistically understand and functionally inhibit critical palmitoylation events. Structural biology methods are readily available to the group and comprise NMR, X-Ray, EM and MS. A highly collaborative working environment allows to adapt the requirement for individual methods to the needs of the project.

Job description:
The major goal of the thesis is to mechanistically understand how substrate proteins are recognized by individual DHHC enzymes. Mechanistic findings will then be interrogated functionally in T cells in collaboration with the laboratory of Britta Brügger of Heidelberg University (https://bzh.db-engine.de/group/69/britta%20br%C3%BCgger). The activity serves to improve one's own academic qualifications. Participation in research and teaching are expected.

Requirements:
Completed university degree (Master) in biochemistry, biology or related areas.

Desirable:
Candidates are expected to have a good understanding and an experimental background in protein biochemistry and/or structural biology. Previous experience in the field of expression of recombinant proteins using bacterial, insect cell and/or mammalian cell expression systems is advantageous. Since the project is part of a large and active trans regional consortium (https://trr186.uni-heidelberg.de/), the successful candidate will be part of a research endeavor that has the overarching goal to unravel the molecular switches that govern cellular behavior. Annual PhD retreats between Heidelberg and Berlin students of the consortium guarantee the candidate to be part of a scientific community that addresses seminal aspects of modern biology. Applications should comprise study records, the name of two reviewers for letters of recommendation, a motivation letter, and a CV, stating the reference: Freund Palmitoylation TRR186 and are to be sent to: chfreund@zedat.fu-berlin.de and steffen.daehn2@fu-berlin.de