The Üstün lab receives funding to study the “Manipulation of protein translation by pathogenic bacteria”. Postdoc and PhD positions are available.
Protein homeostasis embodies a delicate balance between protein synthesis and breakdown, representing the dynamic cycle of protein “life and death.” About one-third of newly formed proteins undergo degradation. Consequently, the processes of protein translation and turnover are rigorously controlled to uphold cellular function and viability. Hence, regulating protein homeostasis in reaction to environmental cues has become a crucial strategy to manage disturbances spanning from aging to pathological conditions in both animals and plants. To allow rapid, versatile, and cost-efficient responses to sudden environmental changes, eukaryotes utilize reversible translational arrest caused by compartmentalization of transcripts in cytosolic membraneless aggregates formed by phase separation. One such type of aggregates are processing bodies (PBs), dynamic ribonucleoprotein aggregates conserved among eukaryotes. PBs are involved in translational arrest, mRNA decay and both RNA and protein quality control and regulate several developmental processes and responses to abiotic stresses. However, our knowledge of how and under which conditions PBs are formed as well as if PBs are hijacked by pathogens to manipulate protein translation is unknown.
Our team aims to delve deeper into how pathogens disrupt this mechanism. Through the generous support of approximately 565,000 euros from the Boehringer Ingelheim Foundation, as part of the “Rise Up!” funding program, the project is set to commence on August 1, 2024, and span a duration of three years.
Human pathogens like salmonella or legionella, as well as viruses, have been demonstrated to impact protein synthesis. Initial investigations led the Üstün lab indicate that plant pathogenic bacteria similarly influence protein synthesis, with this alteration being implicated in disease progression. In our upcoming project titled “Manipulation of protein translation as a virulence strategy of pathogenic bacteria,” we aim to further explore this phenomenon. To this end we have advertised a Postdoc and a PhD position. The postdoc will focus on how PBs are hijacked by bacterial infection to alter global protein translation and what mRNAs are sequestered and repressed in translation. The PhD candidate will address how bacterial effectors induce the formation of PBs to understand the mechanism of PB assembly and analyse the composition of PBs during infection. More details about the positions, requirements and deadlines for application can be found in the job adverts. Apply if you are interested in proteostasis and would like to work in an international, innovative and inclusive team!
All in all, through this endeavor, we anticipate elucidating the comprehensive understanding of how proteostasis, specifically at the level of protein translation, governs immune responses and is consequently manipulated by pathogenic bacteria. Grasping the underlying molecular intricacies of translation modulation in disease settings will pave the way for innovative approaches to tackling diseases and environmental adversities.
Our first review that appeared in 
In our second invited review in 
Which brings us to our latest published preprint “ER-anchored protein sorting controls the fate of two proteasome activators for intracellular organelle communication during proteotoxic stress”, the SFB1101 funded PhD work of Gautier Langin. As proposed in our review about the proteasome and its role in plant immune reactions, we tried to decipher how proteotoxicity, caused by pathogens, diseases, organelle stress, and Co. is regulated. We show that the proteasome autoregulatory feedback loop acts as a gatekeeper to facilitate the communication between nucleus and chloroplast. In our study we revealed that the ER-anchored protein sorting system (ERAPS) controls the proteasomal degradation or nuclear translocation of proteasome activators NAC53 and NAC78. While both transcription factors activate the proteasome gene expression, they repress photosynthesis-associated nuclear genes during proteotoxicity. It appears that this trade-off is highly “conserved” as other stress conditions and developmental cues also lead to similar responses. We think that our findings also provide a new conceptual framework for understanding the integral role of transcription factors in managing cellular proteostasis under environmental stress, suggesting conservation of these mechanisms across kingdoms. But this is just a small summary and teaser 🙂 We promise it will be a good read over the Christmas holidays, lots of data, and possible future implications on other trade-offs between the proteasome and energy metabolism.
Full of hopes we started 2021, posting our first preprint on
Managing a lab with various lab members and different projects is already challenging. Recruiting new team members to start their new projects is always a difficult task. The pandemic doesn’t make it easier. Nevertheless, beginning 2021, we started our search, and with the help of the entire lab we found new members, Shanshuo Zhu and Shiji Hou, to kickstart the ERC project DIVERSIPHAGY. Shanshuo and Shiji have promising results in their projects so far, and we hope to continue this in 2022. We also started a completely new project on the role of “P-Bodies in bacterial infection” with Manuel Gonzalez Fuente, who joined our lab as a postdoc with his own DFG funding from the Walter Benjamin Programme. All in all, it is great to see the group growing, different projects progressing and developing, even though we had limited space in the lab (thanks to the pandemic). The new year will again bring some changes to our group: We are very happy to welcome another postdoc in the new year, Margot Raffeiner (former PhD student in the Börnke Lab), who will join our ERC team, working on the autophagy degradome. Sadly, Shiji had to leave our lab by the end of the year, and we are currently trying to find a new postdoc to study plant microbiome and its influence on degradation pathways (you can find the ad 
Regarding grants for our lab, the year was pretty much focused to get approval for our project (“Specificity of proteasome regulation during plant immunity”) in the 
Usually, in the pre-pandemic era, we would report about exciting meetings, international conferences, and networking events as well as huge social events. Especially not having any international conferences is affecting early career researchers a lot: It is crucial to present your science, to meet new people (future employees, collaborators, friends). Some of our lab members never went to international conferences. This is an essential part of building your own network and preparing yourself for your future. As much as online conferences are a great distraction, and a way to communicate your science (if you don’t present only published things), it misses the “social” part as most social interactions on Zoom or other platforms are impersonal. Our own lab meetings and journal clubs improved a lot when we started having in person meetings again. Our highlight of an in-person meeting was in November, when Yasin Dagdas, group leader at GMI Vienna, visited us, to participate in Gautier’s thesis advisory committee. We had great discussions about Gautier’s PhD project and future publication strategy that helped him a lot to focus his research. We hope for 2022 to have more in person meetings and small conferences.
My talented and super motivated PhD student Jia Xuan Leong joined our lab last year as a master student and was able to show that, in contrast to Pseudomonas, Xanthomonas blocks autophagy in an effector-dependent manner to enhance its pathogenicity. We then went on and screened a couple of effectors for their ability to block autophagy. We analysed XopJ, XopS and XopD, as they have known effects on proteolytic degradation pathways and of course included XopL, because of its ability to interact with SH3P2. Fortunately, it turned out that XopL is able to suppress autophagy which made us very confident that we have to further characterize its function. However, our major concern was that previous reports stated that XopL is not a major virulence fac
Fortunately, with the help of Mary Beth Mudgett and her amazing lab, we were able to show that XopL is one of the major virulence factors r
Meanwhile we got a bit confused, as we realized that XopL is also degraded by autophagy. XopL associates with selective autophagy receptor NBR1/Joka2 which mediates the degradation of XopL. So far NBR1/Joka2 was known to degrade aggregates (aggrephagy), viral proteins and intracellular pathogens (xenophagy) but not bacterial effector proteins. We further discovered that XopL undergoes self-ubiquitination in vitro and in planta, at Lysine 191. Although, mutation of this lysine stabilizes XopL, XopL is still ubiquitinated in plants. We assume (and have also indications) that other lysines within XopL are ubiquitinated.
