From Doubt to Discovery: A 15-Year Journey into Proteostasis, Pathogens, and Persistence

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More than 15 years ago, during my PhD, we stumbled upon something unexpected. In a yeast two-hybrid screen, bacterial effector proteins from Xanthomonas and Pseudomonas interacted with a subunit of the proteasome.

At the time, this wasn’t the kind of result we had hoped for. We were looking for something more obviously tied to plant immunity. I still remember my supervisor not being particularly excited about it. But somehow, I was.

That moment marked the beginning of a long-lasting fascination. I became deeply interested in protein degradation, ubiquitination, and the proteasome, this highly conserved and essential machinery present across kingdoms. The idea that pathogens would target such a fundamental system made intuitive sense to me. After all, the proteasome regulates countless cellular processes, including the turnover of immune components.

But there was a paradox.

The proteasome is not just important – it is indispensable. Disrupting even a single subunit can collapse the entire complex, leading to severe developmental defects or lethality. So why would pathogens target something so fragile? And more importantly, how could they manipulate it without completely destroying their host?

Back then, my thinking was rather radical: perhaps pathogens don’t always aim for precision. Maybe they initially trigger a catastrophic imbalance, benefiting from the chaos, and only later “move on” as the host deteriorates. In contrast to viruses, which depend on living hosts, many bacterial pathogens might tolerate (or even exploit) such damage.

Fast forward to today, and it’s remarkable to see how this idea has evolved. Over the years, numerous studies, including our own review (Langin et al., 2023), have shown that pathogens across kingdoms target the ubiquitin-proteasome system. What once felt like a niche observation is now widely accepted. Looking back, that realization brings both validation and relief, especially after years of skepticism by others.

Enter Autophagy – and the NAC Story Begins

Then came the next wave: autophagy. Suddenly, this second major degradation pathway moved into the spotlight. Like many others, we became fascinated by it. And again, the pattern emerged, pathogens targeting autophagy across bacteria, fungi, oomycetes, and viruses.

This is where our NAC story begins.

We were interested in how the proteasome and autophagy might intersect. While studying proteaphagy, the autophagic degradation of proteasomes, we noticed something puzzling: despite signs of degradation, proteasomes never seemed to fully disappear during infection.

Why?

The answer began to emerge in 2016, when NAC53 and NAC78 were identified as transcription factors regulating proteasome gene expression under stress. This sparked a key idea: if pathogens suppress proteasome activity, could they simultaneously induce its re-synthesis via NACs? That would explain why we never observed complete depletion.

A “Simple Project” That Wasn’t So Simple

When I started my own lab, I thought this would be a small, straightforward project, something “cute” to explore with a modest grant. Fortunately, we received funding through SFB1101, and even more fortunately, Gautier Langin joined the lab as a PhD student.

Gautier quickly generated exciting results. Indeed, bacterial infection induced proteotoxic stress, and NAC53/78 were required to sustain proteasome gene expression. At that point, we had a solid story.

We could have stopped there.

But Gautier didn’t.

Instead, he noticed something unexpected in his transcriptome data: a large cluster of photosynthesis-associated nuclear genes was strongly affected. I remember telling him, quite confidently, that this must be indirect, just a secondary effect.

He disagreed.

Gautier insisted that this might be a direct regulatory mechanism. We made a deal: if he could prove direct targeting, he could pursue this direction fully.

A few months later, he came back with compelling evidence: NACs directly binding to the promoters of these genes. He was right. I was thrilled, not only by the discovery, but by his persistence and scientific intuition.

A Broader Principle Emerges

From there, the story expanded. Gautier explored whether this mechanism extended beyond infection. What he found was striking: diverse stress conditions triggered a similar trade-off, activation of proteasome genes alongside repression of photosynthesis.

This suggested a broader principle: a conserved proteostasis response balancing cellular survival and energy allocation under stress.

Our work points toward a new conceptual framework, where transcription factors like NAC53/78 orchestrate this balance, integrating environmental cues into coordinated cellular responses. And importantly, this mechanism may extend beyond plants.

The Long Road to Publication

We began writing the manuscript during a major transition, moving the entire lab at the end of 2022. In hindsight, we were overly optimistic about timelines. The move delayed us by nearly a year.

Eventually, we submitted to a top-tier journal. The reviews were mixed. Two reviewers were constructive, but one was highly critical and, in parts, misunderstood key aspects of our work. We basically lost a year.

It was a difficult phase.

We spent months strengthening the manuscript, especially the genetics, and refining the story. But persistence paid off. We submitted to Molecular Cell and after roughly a year of revision, the manuscript was accepted.

You can read it here:
https://www.cell.com/molecular-cell/fulltext/S1097-2765(26)00238-8

Beyond the Paper

During this intense period, Gautier reached several major milestones. He completed his PhD in Tübingen, advanced new research directions on proteasome evolution (stay tuned, something pretty cool is coming!) and moved to Vienna to join the Gross lab. Most impressively, he secured his own Marie Curie Fellowship!

What Stays

Looking back, what stands out most is not just the science, but the journey. From a seemingly unexciting yeast two-hybrid hit to a conceptual framework linking proteostasis, stress, and transcriptional control. From doubt and skepticism to validation. From a “small project” to a multi-year effort culminating in a major publication.

And above all, seeing a young scientist grow, developing independence, creativity, and confidence, is perhaps the most rewarding part of this profession.

If there is one lesson from this story, it is this: sometimes the most unexpected findings are the ones worth following the longest.

From Doubt to Discovery: A 15-Year Journey into Proteostasis, Pathogens, and Persistence Read More »

Our journey to publish our P-body paper

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Everything started maybe 9 years ago, during my postdoc in Sweden. My colleague and friend Anders Hafrén, now also a group leader working on P-bodies and stress granules during viral infection, had a couple of leftover DCP1 plants – a P-body marker, from his last experiment.

When he told me “just put your Pseudomonas on it” and “see what happens”, I was honestly a bit like—why would I do this? I was not interested in condensates storing mRNA. I was all about autophagy and proteasomal degradation and their roles in plant immunity.

But Anders insisted. He said this will become huge, and that there is an interplay between degradation machineries, P-bodies, and RNA biology in general. He already saw it back then.

Figure 1: First ever P-body quantification

Convinced, but also curious, I used some extra confocal time. This time not imaging my autophagosome “dotties” (which were always a nightmare in leaf tissues…), but bright P-body condensates. And wow – indeed, Pseudomonas actively modified them. Their number increased after 24 hpi (Figure 1).

So the question became: could bacterial pathogens hijack this pathway – and why?

At that time, still focused on degradation, I thought maybe P-bodies are recycled via the proteasome or autophagy, explaining their altered numbers. I went back to my proteomics data and realized that one component associates with ATG8. Could it be that Pseudomonas, by activating autophagy, recycles P-bodies? But I wasn’t fully convinced. The strong increase in P-body foci didn’t quite fit with what we knew about Pseudomonas-triggered autophagy. So I stepped away from the idea, keeping it only as a small side project. But that’s where it initially stalled. Apart from a few preliminary experiments, showing that P-body induction depends on bacterial effector delivery and hinting at interactions between autophagy components and DCPs, we didn’t pursue the project further, as we shifted our focus to other promising directions.

And then things changed.

When Manuel González-Fuente decided to join the lab with his own fellowship after finishing his PhD, I proposed several projects, but this one immediately caught his interest. It was novel, ambitious, and risky. After many discussions, grant writing, and nearly a year of waiting, Manuel secured his DFG fellowship and started working on P-bodies during bacterial infection. From there on, we fully committed to this fascinating but also enigmatic compartment. The beginning was not easy, many experiments didn’t work, we had setbacks, and progress was slow. Even our move to Bochum cost us almost a year of experiments.

But we didn’t give up.

Instead, we kept going analyzing -omics data, refining ideas, and this is when the link between ER stress and P-bodies started to emerge. Manuel presented his exciting project at several conferences, received prizes, awards and encouraging feedback. Eventually, all in all it felt like the first “season” of the story came together, and Manuel started writing the paper, which we preprinted more than a year ago.

Then the real gamble began.

We were excited to be reviewed in a top journal, but quickly realized how tough the process would be. We didn’t give up and eventually submitted the manuscript to Science Advances.

Figure 3: Pseudomonas does not induce stress granules.

After multiple rounds of revision (and moments where it really looked like we wouldn’t make it), the paper was finally accepted. If you wanna read it you can find it here: https://www.science.org/doi/10.1126/sciadv.aec4477#  Huge credit here to Manuel: he always believed in the story, even at times when I had doubts and felt very low (also due to another manuscript that we have been trying to publish since two years – wait for this Thursday!)

Looking back, some, but not all, reviewer feedback actually helped us improve the manuscript and led to additional insights—for example, that Pseudomonas specifically induces P-bodies without triggering stress granules (Figure 2).

So what about season 2? 🔬

There are still many open questions we are now actively working on:

Which mRNAs are selectively repressed in P-bodies? A question Manuel and I have been asked so often when presenting our work at conferences. We will soon conduct polysome profiling and Ribo-seq experiments across different genotypes during bacterial infection.

How exactly does ER stress control P-body assembly? We finally have the genetic material to address this—and a small teaser: P-body assembly depends on transcription factors that regulate ER stress – Manuel and his talented Bachelor student Nea Khalo are currently investigating this.

What defines selective autophagic turnover of P-bodies? This is a hidden gem in our manuscript. We believe we have identified the selective autophagy receptor, and likely also the E3 ligase mediating the degradation of P-body components—but this is still ongoing work that PhD candidate Wentao Luo is trying to solve.

How does HopN1 suppress translation if it is not dependent on P-bodies? For this, we already performed proteomics experiments ~4 years ago in Tübingen and identified several proteins involved in translation regulation and ribosome stalling. Manuel will now continue to follow up on this now that his paper is finally published 😊

Figure 3: Pseudomonas inhibits TOR activity.

How does Pseudomonas inhibit TOR activity? We do not know whether this is dependent on effector proteins or simply the pathogen turing source tissue into a sink (Figure 3). We have some hints that effectors can indeed interact with TOR and manipulate its “properties”. More to come in the future.

 

What is the role of P-bodies in abiotic stress, and how are they regulated by posttranslational modifications? We have become particularly interested in whether distinct or shared modification signatures control P-body dynamics under different stress conditions, something Thorben Krüger is now beginning to explore.

Final thoughts

This journey would not have been possible without the people behind it.

A very special thank you to Manuel González-Fuente, for his persistence, curiosity, and resilience. He drove this project through 5 years of challenges, setbacks, and revisions, and never lost belief in the story, even when things were not working at all. This paper is a testament to his dedication.

And of course, huge thanks to all co-authors, collaborators, and lab members who contributed along the way, this was truly a collective effort 🙌🌱

Şuayb

Original publication:

Manuel González-Fuente et al.: Bacteria Use P-body Condensates to Attenuate Host Translation During Infection, in: Science Advances, 2026, DOI: 10.1126/sciadv.aec4477

Our journey to publish our P-body paper Read More »

Autophagy acts as a spatial organizer of cell-type-specific plant immunity

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To prevent frequent outbreak of diseases, plants have acquired a complex and multi-layered immune system. Cell surface immune receptors recognize conserved pathogen-associated molecular patterns (PAMPs) and initiate basal defences, known as PAMP-triggered immunity (PTI), while intracellular receptors activate effector-triggered immunity (ETI). Over the past years, this view has evolved toward a model of mutual potentiation, where PTI and ETI reinforce each other to generate robust defence. Yet one fundamental question has remained unresolved: how are these immune responses coordinated across the highly heterogeneous cellular landscape of a leaf?

Our study (you can find it now on the biorxiv server: https://www.biorxiv.org/content/10.64898/2026.04.06.716646v1)  led by our amazing postdoc Shanshuo Zhu provides a compelling answer by positioning autophagy, not simply as a degradation pathway, but as a spatial organizer of immunity across cell types. Our findings try to decipher the long-standing controversial role of autophagy as a pro- or anti-immunity factor: autophagy partitions immune responses between cell-types, aligning defence outputs with cellular context.

Resolving a long-standing paradox

Autophagy has been implicated in contrasting roles during plant-microbe interactions, promoting susceptibility in some contexts while enhancing resistance in others or restricting cell death. This ambiguity has persisted for over a decade, largely because most studies treated the leaf as a homogeneous tissue. Advances in single-cell RNA sequencing have opened new avenues to resolve cell-type-specific responses, an essential step for understanding Pseudomonas infections that enter through stomata and establish within the mesophyll.

By combining single-cell transcriptomics with cell-type-specific complementation approaches, we reveal that this paradox dissolves when spatial context is considered. Autophagy exerts distinct, even opposing functions in different cell-types, likely explaining conflicting observations in the literature.

Guard cells: facilitating pathogen entry

At the leaf surface, guard cells form the first line of defence by closing stomata to prevent bacterial invasion. Intriguingly, our study shows that autophagy actively promotes early stomatal re-opening during infection, thereby facilitating pathogen entry.

Mechanistically, this process is linked to the vacuolar recycling of the ABA receptor PYL4. By targeting PYL4 for degradation, autophagy dampens ABA signalling, which would otherwise maintain stomatal closure. In autophagy-deficient plants, elevated ABA signalling prevents re-opening, restricting bacterial entry.

This finding reframes autophagy as a pathway that pathogens may exploit early during infection – not by directly suppressing immunity, but by modulating physiological gatekeeping at the tissue interface.

Mesophyll: restraining and enabling immunity

Once bacteria bypass the stomatal barrier, the battleground shifts to the mesophyll. Here, autophagy plays a fundamentally different role. We initially hypothesized a mesophyll-specific role, as autophagy-deficient mutants exhibited severe phenotypes, such as chlorosis and tissue collapse upon syringe infiltration, likely originating from mesophyll cells.

Our scRNAseq analysis revealed that loss of autophagy leads to a pre-activated immune state, characterized by elevated expression of key regulators such as the EDS1–PAD4–ADR1 node. At first glance, this might suggest enhanced resistance, possibly also explaining the severe phenotype after infection. However, our investigation reveals a striking uncoupling: despite elevated immune signalling, canonical PTI outputs, such as ROS production and transcriptional responses, are impaired.

This disconnect leads to a central conceptual advance:
immune activation alone is not sufficient for effective defence.

Instead, autophagy appears to maintain the functional integrity and spatial organization of immune signalling networks, ensuring that activation translates into execution. Without it, signalling becomes misregulated, amplified yet ineffective.

We are currently trying to deliver the final evidence that this is indeed driven by the cell-type specific role of autophagy.

A spatial model of immune coordination

Taken together, our work supports a model in which autophagy orchestrates immunity across different cell-types:

  • Guard cells: autophagy promotes pathogen entry by enabling stomatal re-opening
  • Mesophyll cells: autophagy constrains and organizes immune signalling to ensure effective defence response

This dual role transforms autophagy into a spatial coordinator, aligning immune strategies with tissue-specific demands.

Implications for PTI-ETI potentiation

The findings also offer a fresh perspective on PTI-ETI interplay. The impaired PTI outputs observed in autophagy mutants provide a plausible explanation for previously reported defects in ETI-associated responses, including EDS1-dependent hypersensitive cell death. Here, we are also looking into final experiments to validate a cell-type specific role for autophagy in this process.

Our current working model suggests that autophagy may be required but for maintaining the conditions under which PTI and ETI can effectively potentiate each other. EDS1 may play a central role in it, since it has been shown to be an autophagy target, being essential to constrain immune signalling (Clavel et al., 2024).

Beyond degradation: toward proteostasis-driven immunity

In summary, our study reinforces an emerging view of proteostasis pathways as central regulators of immunity explaining why pathogens love to hijack it – see also our recent review article “Every step you take: How pathogens hijack host proteostasis“.

Our findings raise several intriguing questions:

  • How is autophagy itself spatially regulated during infection?
  • Do pathogens actively manipulate autophagy in a cell-type-specific manner?
  • Would this explain contrasting functions of effectors from the same pathogen inhibiting or activcating autophagy?
  • Can spatial control of proteostasis be engineered to enhance crop resistance?

By integrating single-cell resolution with genetics and cell biology, we established a unifying framework:

Plant immunity is not only multilayered but also spatially partitioned-a concept recognized for decades—and autophagy emerges as a key organizer of this architecture.

Autophagy acts as a spatial organizer of cell-type-specific plant immunity Read More »

Oops, I did It Again: Bacteria Remixing Host Translation!

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In the ongoing battle between pathogens and their hosts, an intriguing dynamic unfolds at the cellular level, revealing how bacteria can subtly undermine host defenses. Recent research conducted by #theustunlab postdoc Manuel González-Fuente and colleagues at Ruhr-University Bochum sheds light on the sophisticated strategies employed by the bacterium Pseudomonas syringae to manipulate host translation during infection, providing a novel perspective on plant immunity. You can find our preprint ” Bacteria use processing bodies condensates to attenuate host translation during infection” on bioRxiv.

A Dual Attack on Translation

Our study demonstrates that Pseudomonas syringae (Pst), utilizes two bacterial effectors that exhibit liquid-like properties to induce the formation of plant processing bodies (P-bodies), ribonucleoprotein condensates integral to the regulation of RNA metabolism and translation. This manipulation serves to attenuate the host’s protein synthesis at a critical juncture when the plant needs to mount an adequate defense.

By targeting ribonucleoprotein condensates, Pst effectively disrupts the delicate balance of protein homeostasis within the plant. We uncovered that Pst’s repression of the endoplasmic reticulum (ER) stress response is a prerequisite for P-body assembly, a finding that highlights the intricate connection between stress responses and translation regulation.

P-Bodies and Autophagy: A New Intersection

A groundbreaking element of Manuel‘s work is the identification of a novel intersection between P-bodies and autophagy. Autophagic processes, typically known for their role in degrading cellular components, emerge as crucial players in managing P-body dynamics. We found that the clearance of P-bodies via autophagy is essential for maintaining a balance between active and inactive mRNAs. This presents a compelling narrative of how pathogens may exploit fundamental cellular pathways to subvert host responses.

Implications for Plant Immunity

The findings carry significant implications for understanding plant immunity and the ongoing arms race between pathogens and their hosts. By demonstrating that specific P-body-inducing effectors (such as HopM1 and HopN1) can suppress translation, our study emphasizes the potential for these bacterial effectors to be exploited as tools for further research into immune regulation. It raises pertinent questions about which mRNAs are affected in translation efficiency and how these components potentially contribute to the host’s susceptibility or resistance to infection. Our results show that P-bodies are involved in the posttranscriptional control of gene expression of certain immune components, indicating that Pst attenuates plant translation as a virulence strategy to dampen plant immunity.

Looking Ahead: Future Research Directions

As the field of plant pathology advances, Manuel‘s work sets the stage for future explorations into bacterial manipulation strategies. It opens new avenues for investigating how other pathogens may employ similar tactics to compromise host translation and immune responses. Additionally, understanding the mechanisms governing P-body assembly and their role in RNA metabolism could pave the way for novel strategies targeting bacterial infections in crops. In conclusion, our research not only unveils a sophisticated bacterial strategy to dampen plant immunity but also enriches our understanding of the complex interplay between translation, stress responses, and autophagy in cell biology.

References: González-Fuente et al., “Bacteria use processing body condensates to attenuate host translation during infection“, 2025 bioRxiv 2025.01.09.632196; doi: https://doi.org/10.1101/2025.01.09.632196

Oops, I did It Again: Bacteria Remixing Host Translation! Read More »

Bye bye toxic relationships: the year of BRAT is over – welcome demure 2025!

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It’s one of the last days of 2024, a year full of surprises, challenges, toxic relationships, proud and sad moments. Did we achieve our goals? No, unfortunately not. It has been a year full of disillusionment in many aspects. But it has been also a year full of new beginnings, small success stories and preparing us for bigger things that will hopefully follow in 2025.

Some general reflections on daily modern dynamics and decisions for 2025:

In today’s world, resentment and jealousy seem to prevail everywhere. Instead of focusing on our own “business”, we often get caught up in scrutinizing others’ work, fueling unnecessary competition and division. The lack of teamwork, coupled with egoism, creates a toxic atmosphere where collaboration becomes a rare commodity.  Sadly, this isn’t just a social media phenomenon—it’s embedded in our everyday interactions. Sad moments of misunderstanding and miscommunication are no longer isolated events but widespread occurrences. It seems like many people want to misunderstand each other on purpose – to do what? complain? spread toxicity? Or to try to “defeat” each other? It appears to be a total waste of energy.

Why do we spend so much time entangled in others’ affairs instead of concentrating on our own growth and contributions? Misinterpretation and judging without understanding the person or the context only deepen the divides, fostering toxic relationships. Social media platforms like X (formerly known as Twitter) exemplify this behavior in many ways. As such, we will not support any form of toxicity on any platform. It is sad to witness how a once-enjoyable platform like Twitter—where individuals could freely share opinions, spark meaningful discussions, and even foster scientific enthusiasm—has devolved into a place of hate and toxicity. During the past years, thanks also to these platforms, many people realized that #Inclusion, #diversity, & #equality are crucial aspects of our lives & have  become integral in academia. However, while we advocate for this, many people face more and more discrimination, bullying and toxic behavior. As a result, we have chosen to disengage from actively participating on this platform. Moving forward, we will limit our presence there to sharing publications, lab news and job advertisements only.

Yes, we faced some disillusionment, but what else did 2024 bring to #TheUstunLab?

Despite moments of disillusionment and some disappointments, 2024 has been an incredibly productive year for us. One of our major accomplishments has been the establishment of a faculty-wide confocal microscopy platform, spearheaded by Üstün Lab postdoc Manuel González Fuente. The platform is already being utilized by more than 30 researchers from seven different groups across the faculty. We’re both proud and delighted to have successfully launched this initiative and look forward to growing it further in the future. We hope that other groups will follow suit, as diverse and impactful research can only thrive with access to a variety of cutting-edge platforms and facilities.

Research Highlights

This year has been challenging in terms of our scientific output, with some setbacks along the way. Unfortunately, we have yet to publish our major story from Gautier Langin (2023/2024), titled “ER-anchored protein sorting controls the fate of two proteasome activators for intracellular organelle communication during proteotoxic stress“. However, after thorough revisions, we are optimistic about submitting this work again in 2025.

In parallel, we have been finalizing Manuel’s manuscript, which explores how pathogens manipulate protein translation by targeting processing bodies (protein-mRNA condensates). Here’s a little teaser: the study is packed with exciting findings on condensating effectors, protein translation, the interplay of processing bodies and ER stress, and more.We aim to preprint this work in the first weeks of January 2025. Another exciting project is Shanshuo’s postdoc paper, which uncovers how cell-type-specific autophagy responses shape plant-pathogen interactions. A sneak peek: stomata play a crucial role!

Beyond these individual projects, we’ve had the pleasure of collaborating with some incredible labs this year. In partnership with the labs of Alyona Minina, Simon Michaeli, and Yasin Dagdas, we’ve contributed to some exciting studies on autophagy and proteotoxicity. Working with friends and colleagues on collaborative projects is always a highlight, and we’re eager to continue fostering these relationships in 2025 and beyond. While the year has had its share of challenges, we are proud of the progress we’ve made and excited about what lies ahead. Onward to 2025!

Proud moments in 2024:

Although we may not have published as much as we had hoped, the members of #TheUstunLab have achieved remarkable success this year. Every team member actively participated in national and international conferences, showcasing their work through posters and talks.

    • 37th Molecular Biology of Plants Conference, Germany (Gautier, Talk)

    • International CRC1101 Symposium, Germany (all group members)

    • Plant Macro-and Microbiomes COS-EMBL Workshop for early career scientists (Margot and Manuel, Talks)

    • Plant Biology ASBP in Hawaii, USA (Margot and Manuel, Poster – Associate Featuring Editor meeting with editorial boards of Plant Cell and Plant Physiology)

    • Protease Meeting , Germany (Margot, Talk)

    • MadLand Anuual Meeting, Germany (Gautier, Talk)

    • ENPER, Portugal (Ophélie, Talk)

    • Plant Proteostasis conference in Vienna, Austria (all group members, Poster)

    • New Phytologist Symposium: Stomata, China (Shanshuo, Poster and Flash talk)

We were thrilled and proud to see our lab members recognized for their outstanding work this year. Manuel and Shanshuo received poster prizes, and Margot was honored with a talk award for her presentation at the Protease Meeting in Hohenheim.

We are growing: theÜstünLab receives funding to study processing bodies:

Another award for our lab came in form of additional funding for the continuation of Manuel’s project on processing bodies: Thanks to his great preliminary work and findings we were able to  secure more funding to study how pathogens manipulate protein translation by targeting processing bodies (https://news.rub.de/english/2024-04-16-new-project-how-pathogens-disrupt-protein-synthesis-plants). Our team is committed to further exploring how pathogens disrupt this critical mechanism. With the generous support of approximately €565,000 from the Boehringer Ingelheim Foundation’s “Rise Up!” funding program, we are excited to advance our research in this area. To support this effort, we welcomed Thorben Krüger as a postdoc and Wentao Luo as a PhD candidate. We are delighted to have these talented new members join us, further strengthening our “Protein Translation Unit.”

Other activities: from teaching and other highlights of the year

In 2024, we remained deeply involved in teaching activities. The members of TheUstunLab supervised four students during rotation modules, three bachelor theses, and one master thesis. We were particularly thrilled that Nazife Aydin and Nico Schulz completed their bachelor theses with outstanding results. It was truly a joy to introduce our students to the scientific principles and philosophy of our lab, and incredibly rewarding to witness their growth into the next generation of scientists.

This year, our own 5-week course, “Plant Cell Biology Meets Plant-Pathogen Interactions”, organized by Manuel and Suayb, gained even more attention. We decided to expand the course, accepting 10 students instead of the usual 6. Over the five weeks, students engaged in lectures on plant-microbe interactions, fundamental plant cell biology, experiments on proteostasis and plant immunity, and a fantastic seminar that explored recent papers in the field.Although teaching was demanding and exhausting, we thoroughly enjoyed the experience, particularly the opportunity to engage with the enthusiastic and talented bachelor and master students at RUB. We observed that smaller course formats foster faster learning, as students benefit from closer interactions with their supervisors and the ability to ask questions at any time. It is part of our lab’s philosophy to have close interaction with students, taking away the distance that academic teaching can create sometimes.

We are excited to expand our teaching responsibilities in 2025 and continue with our course, while also taking on new teaching opportunities. Additionally, we look forward to welcoming more bachelor and master students into our lab! While the workload is substantial, witnessing students’ growing passion for science and watching them evolve into future scientists is immensely rewarding.

Other highlights of the year:

    • Many happy hours in the faculty organized by Paul Gouguet

    • Visit to south tyrol and the institute in Laimburg

    • Being under review in one of the CNS journals

    • Lab visit to Tübingen and Vienna

    • Faculty party and our self-organized cocktail bar (too many Aperols)

    • Spain winning against Germany during the faculty party

    • Linus’ lab training in summer

    • Christa’s scientific visit to study phytoplasma effectors and their role in proteostasis

    • Chinese hotpot event with the lab (food coma)

    • Christmas potluck (food and glühwein coma)

Concluding remarks

Indeed, it has been an intense, exhausting, yet sometimes exciting and rewarding year for our team. We are relieved to close the chapter on 2024 and look forward with hope that 2025 will bring positive news and experiences. The coming year promises to bring new adventures, significant changes, and challenges for the Üstün Lab, but we have no doubt that our incredible team will tackle them together with determination and resilience. This year has been a journey of growth and learning. We’ve embraced persistence, learned to accept and stay true to ourselves, and mastered the art of ignoring toxic distractions to focus on our own work.

On that note: we wish everyone a joyful New Year and a fantastic start to 2025, from all of us at the Üstün Lab!

Bye bye toxic relationships: the year of BRAT is over – welcome demure 2025! Read More »

The Üstün lab receives funding to study the “Manipulation of protein translation by pathogenic bacteria”. Postdoc and PhD positions are available.

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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.

 

The Üstün lab receives funding to study the “Manipulation of protein translation by pathogenic bacteria”. Postdoc and PhD positions are available. Read More »

A year end summary: As Britney once sang “…but now we are stronger than yesterday (2023), now it’s nothing but our way…”

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Reflecting on the passing year, 2023 has been a year of transformation and challenges that hopefully made us stronger than ever. Let’s begin with some unfiltered truths. Our journey this year was far from smooth, marked by transitional hurdles.

Our new lab at RUB in June 2023

Moving an entire lab from one place to another, including almost all lab members was a major challenge that brought us to our own limits. Major delays, considering wet lab work (e.g., we’ve been waiting more than six months for our water taps in our lab, to be able to normally work in it) and office place (Suayb got his office one year after his arrival), navigating a new environment, and grappling with shifts in administration and colleague dynamics made this year a test of resilience for all of us. Transitioning from the vibrant and forward-thinking environment of ZMBP in Tübingen, it was evident to all of us that our experience in Bochum would offer a “unique” perspective and bring about notable differences. Still, it held many surprises, for all of us, even the ones that have been experiencing the “German system” before. One prevailing realization was the nature of hierarchical structures, where departments and domains seemed ingrained. At times, it felt like an uphill battle against this entrenched mindset. But amidst these challenges, there’s a growing understanding that breaking free from these old structures is crucial for progress. At least we slowly got used to everything which is essential to improve and change certain structures. We will see what the future holds for TheÜstünLab!

Unfortunately, challenging times often reveal the genuine nature of human kind. We’ve observed that expressions of gratitude, acts of kindness, and displays of emotional intelligence are regrettably rare. At times, whether glancing through the news or observing our immediate environment, it appeared as though the essence of humanity was fading. We‘ve seen many memes & quotes about that “humanity is dead” – let’s hope 2024 will convince us of the contrary. 2023 left us contemplating the way forward towards cultivating a more empathetic and compassionate society in 2024. In more simple words – let’s just move on.

Manuel is receiving his poster award at MPMI in Providence.

So let’s stop with the unfiltered truth- and move on to the bright side. Amidst the turbulence, there were also bright spots for our lab. Members of the lab have been traveling to various conferences (Paris, Mendel Early Career Symposium in Vienna, 2024 MPMI in Providence, GRC Plant Proteolysis, ICPP in Lyon, invited seminars in Freiburg & Heidelberg) provided invaluable experiences. Manuel‘s poster award at the MPMI conference, catching up with old friends, and forging new friendships within the proteostasis community really brightened up the ride. 

Manuel during his Plant Immunity Lecture.

Another very bright spot was our engagement in teaching at RUB. TheÜstünLab led two plant science courses (one with other plant groups and one on plant-microbe interactions). It has been a very fun and rewarding journey for Manuel & Suayb to organize and supervise the courses. Manuel’s exceptional supervision and active involvement in our lab course, “Plant Cell Biology meets Plant-Pathogen interactions,” marked a significant milestone, positioning TheUstunLab prominently within the teaching landscape at RUB. Encountering the enthusiastic and talented bachelor and master students at RUB filled us with excitement. We’re thrilled to extend our involvement in additional teaching responsibilities in 2024. Furthermore, we eagerly anticipate welcoming bachelor and master students to our lab! It’s a lot of work for us but witnessing students’ growing interest in science and their evolution into prospective scientists is immensely rewarding! By far our teaching experience and interaction with the students have been the highlight of 2023!

Additionally, contributions to research papers, forging new collaborations, and the submission of a major grant, along with the approval of the confocal grant (yes, we have a fancy confocal now!) and Gautier’s preprint, signified progress and promise for future endeavors. You can find more on our research activities here.

As we bid farewell to 2023, it’s not just a year concluded; it’s a chapter filled with lessons, challenges, defeats but also victories. Sad and happy memories, things we simply want to forget and events/encounters we want to cherish. We move forward to 2024, wiser, and more resolute in our pursuit of breaking barriers, fostering community, and advancing research in our shared field. Let’s stay open to the surprises that 2024 has in store for us!

TheÜstünLab

A year end summary: As Britney once sang “…but now we are stronger than yesterday (2023), now it’s nothing but our way…” Read More »

Publish don’t perish! – TheÜstünLab publication activities in 2023

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As 2023 winds down after an incredibly eventful year, the global scientific community is in its familiar rhythm of gathering the fruits of their labor. Researchers worldwide are wrapping up their manuscripts, sending them off to journals, or sharing them on platforms like bioRxiv. Within the last two weeks we have seen many labs preprinting papers, some of them having multiple new exciting stories that will have a huge impact in plant science. Witnessing this evolution within the plant science community is truly remarkable, especially as more scientists embrace the principles of open science by endorsing preprints. Despite the transitions from Tübingen to Bochum and the inevitable hiccups that followed, our momentum still persists. #TheUstunLab has been productive in 2023 and published one research paper, two reviews, one commentary in Nature Plants, two collaborative preprints on nanodomains and plant autophagy

In 2022 and 2023, we have been busy writing reviews about the “Interplay between autophagy and proteasome during proteasome turnover” and “The Plant Ubiquitin-Proteasome as a target for microbial manipulation”.

Our first review that appeared in Trends in Plant Science discusses the intricate relationship between two essential cellular degradation pathways: the ubiquitin-proteasome system (UPS) and autophagy. It highlights their individual roles in maintaining cellular homeostasis by clearing malfunctioning or unneeded proteins and reveals their interdependence, which was historically overlooked. We propose future directions to better understand and dissect the interplay of both pathways.

You can find more details here: https://doi.org/10.1016/j.tplants.2023.01.013

In our second invited review in Annual Review of Phytopathology, we describe how the ubiquitin-proteasome system regulates different immunity-related processes and how pathogens (bacteria, viruses, fungi) subvert this to promote disease. Pathogens use intricate tactics to manipulate the UPS, affecting plant immune responses. They utilize effectors to influence the degradation or stability of proteins involved in plant defense. However, this interplay is complex; the UPS is essential for effective plant defense, yet pathogens rely on its proper function for their pathogenicity. This complexity indicates that our understanding remains superficial. Thus, we propose in our review that it is vital to comprehend how the proteasome and its components are finely tuned at various levels. You can read more here:

https://www.annualreviews.org/doi/10.1146/annurev-phyto-021622-110443

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.

You can find the link here: https://www.biorxiv.org/content/10.1101/2023.12.11.571118v1

If you want to have a quick summary of our paper you can find this on the new biorxiv “addon” ScienceCast (https://sciencecast.org/casts/dypf9lriqtaz) that provides AI-generated summaries for expert and general audience – it is a fantastic tool and surely will help as to disseminate our research.

We are grateful for every feedback, comments and suggestions regarding our manuscript that we will certainly keep in mind before we submit in January 2024. Please don’t hesitate to contact us – we are always happy to discuss science!

TheUstunlab will certainly try to keep its spirit high in 2024 by finalizing papers (e.g., our Autophagy-Auxin-Vacuoles manuscript, cell-type specific autophagy) and participating in collaborative manuscripts on proteostasis (one will appear in the “Compelling Open Questions in Plant Proteolysis Research” in the focus issue on plant proteolysis in The Plant Cell). Hope that all of you won’t have too much stress the days before Christmas and remember: do not submit to journals before christmas 🙂

Happy Holidays to everyone!

TheUstunLab

Publish don’t perish! – TheÜstünLab publication activities in 2023 Read More »

PhD Position in Plant Proteostasis Research

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Our group is still searching for a PhD candidate in the SFB1101 funded project “Specificity of proteasome regulation by tail-anchored transcription factors”. Within this project we have identified two transcription factors that regulate proteasome gene expression during bacterial infection and other proteotoxic stresses (Langin et al., unpublished). Interaction studies with both transcription factors revealed various proteins implicated in their degradation via the ERAD system and trafficking to the nucleus from the ER. Currently, we are looking into additional target genes of these transcription factors as they seem to mediate the trade-off between proteasome activation, growth, and defense.

The project is for three years with a possibility of a one year extension. Starting date is expected to be March or April 2023 but negotiable. Application deadline is the 9.01.2023. We are looking forward to receiving your application with the subject line “Application PhD-SFB1101 ANR: 1379” as a composite pdf-file in English. Please include a letter of motivation with your research interests, CV, name, and addresses of at least two referees via email: suayb.uestuen@rub.de

PhD Position in Plant Proteostasis Research Read More »

Postdoc position available in plant microbiome and autophagy research

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Our group is still searching for a postdoc to continue our ERC funded research on “how the microbiome influences plant autophagy”. In the ERC project DIVERSIPHAGY we want to obtain a holistic picture of the role of autophagy in plant-microbe interactions by utilizing bacterial, genetic, and cellular diversity. So far, we have identified that (i) root microbiota are inducing autophagy in roots and shoots, (ii) commensal bacteria can compensate impaired growth in autophagy mutants and (iii) specific bacteria are enriched/depleted using microbial profiling under autophagy modulated conditions. We would like to continue this project with a postdoc experienced in plant microbiome research who will lead this part of the ERC funded project. PhD candidates with proven expertise in plant-microbiome research are also welcome to apply. The position is for 2 years, with a possibility to prolong it for another 2 years. The position is available immediately and open until a suitable candidate is found. For more details about the position and project see the ad below or contact suayib.uestuen@zmbp.uni-tuebingen.de

Postdoc position available in plant microbiome and autophagy research Read More »