At a glance: introductions to recent FEBS Long-Term Fellows

The 5th FEBS Fellows Meeting in Portugal this summer brought together recent holders of FEBS Long-Term Fellowships to present their research, inspire each other and connect. This post summarizes the research work of some of the Fellows and catches up with their current career paths.
At a glance: introductions to recent FEBS Long-Term Fellows
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Faidon Brotzakis

Bodossaki Foundation Post-Doc Fellow, Yusuf Hamied Department of Chemistry, University of Cambridge, UK (currently collaborating with Institute of Bioinovation, BSRC Fleming, Vari, Greece)
 [email protected]; [email protected] | Personal website | Twitter

Could you discuss with us your postdoctoral work, summarize the main findings of your project presented during the 5th edition of the FEBS Fellow Meeting and explain why it is relevant to our field?

Alzheimer’s disease affects over 40 million people worldwide, with associated annual costs of over $600 billion. It is widely believed that dysregulation of the binding of protein tau to microtubules by aberrant post-translational modifications such as phosphorylation and acetylation is one of the molecular processes most closely linked to the onset and progression of the disease. However, due to the dynamic nature of tau, state-of-the-art experimental structural biology methods (NMR, cryo-EM) cannot fully characterize the atomistic structure of the tau–microtubule complex in order to enable structure-based drug design campaigns. In my postdoctoral project in the group of Michele Vendruscolo at the Centre for Misfolding Diseases (CMD) of the University of Cambridge (UK), we further developed computational structural biology methods to integrate cryo-EM data into molecular dynamics simulations in a time-efficient manner. This technology, named MEMMI (bioRxiv), enabled the simultaneous determination of the tau–microtubule structure and dynamics as well as the prediction of key regulatory (and novel) tau–microtubule stability-altering phosphorylation and acetylation sites occurring in Alzheimer’s disease patients. The work at the University of Cambridge and supported by the FEBS Long-Term fellowship is published in ACS Central Science and bioRxiv. A full list of publications during the Fellowship (2021–2022) is here.

Could you tell us how the FEBS Long-Term Fellowship helped you during your postdoctoral stay?

After my PhD and postdoc in UvA (Amsterdam, the Netherlands) and ETHz-USI (Zurich-Lugano, Switzerland) dedicated to the development of efficient computational methods for determining the dynamics of proteins, I decided to expand my expertise towards integrating cryo-EM structural information into molecular simulations, in order to tackle large protein assemblies of biomedical relevance. The FEBS Long-Term Fellowship stimulated my young academic career by enabling me to join the CMD in Cambridge where such computational integrative biology methods were pioneered. The Fellowship gave me access towards independence through salary and conference funding as well as facilitated building a competitive academic profile and a network of bright collaborators.

Could you share with us what are your long-term career goals and maybe explain what will be the next step for you in your career?

My long-term goal is to establish my own research group in data-driven computational biology towards the aim of efficient discovery of chemical agents for therapeutics. I have recently been appointed a Bodossaki foundation postdoctoral scholarship joint between UK and my home country –Greece – and currently use my competencies, experience and CV towards independence – that is, by writing and applying for several European and national research grants as well as taking up teaching.



Mariia Efremova

Marie Skłodowska-Curie Eurotech Postdoctoral Fellow, Department of Applied Physics and Science Education, Eindhoven University of Technology, the Netherlands
[email protected] | Personal website | Twitter

Could you discuss with us your postdoctoral work, summarize the main findings of your project presented during the 5th edition of the FEBS Fellow Meeting and explain why it is relevant to our field?

The challenge of using magnetic gradient fields for tracking and manipulating genetically defined mammalian cells (magnetogenetics) has been tackled for several decades. The major obstacle in this area is genetically encoded labels of the target cells that need to be receptive to magnetic signals. Overexpressing of ferritin – the most common Fe-storing protein in mammalian cells – has been proposed as a biomagnetic genetic handle. However, detailed calculations show that the magnetic properties of ferritin are orders of magnitude too weak to support suggested mechanisms.

In my postdoctoral project in the group of Gil Westmeyer (Technical University of Munich, Germany), we worked with genetically encoded nanoreactors biomineralizing iron oxide called encapsulins originating from the bacteria Quasibacillus thermotolerans (Qt). We expressed these magnetic nanocompartments in mammalian HEK293T cells, which could then be magnetically sorted at room temperature without an external label. We demonstrated the real-time manipulation of pre-sorted cells with magnetic gradient fields at the tip of the needle. Moreover, we showcased encapsulins as T2 contrast agents for magnetic resonance imaging of HEK293T and HepG2 cell lines.

You can find our studies on the Qt encapsulins in mammalian cells published in ACS Nano here and Pharmaceutics here.

Could you tell us how the FEBS Long-Term Fellowship helped you during your postdoctoral stay?

After defending my PhD thesis in 2018 (Moscow, Russia), one of my goals was a postdoctoral position abroad and a substantial change in my research direction. The FEBS Long-Term Fellowship gave me a unique chance to relocate to Germany within a very short time frame (the proposal was submitted in October and supported in December, both 2018) and join the Westmeyer laboratory at the Technical University of Munich from January 2019. This project allowed me to significantly expand my skill set with the methods of molecular and cell biology, mammalian cells, and protein engineering, as well as biochemistry. I also used the FEBS Long-Term Fellowship as a stepping stone to apply for another independent funding and continued my stay in Germany as a Humboldt Postdoctoral Researcher.

Could you share with us what are your long-term career goals and maybe explain what will be the next step for you in your career?

I would like to become a university professor with my own research group, which will, ideally, create a new technology for non-invasive cell manipulation and tracking based on magnetogenetics. I have recently started a collaborative project between the Eindhoven University of Technology in the Netherlands and the Technical University of Munich. Thus,  my “next” step is fuelling this exciting cooperation of physicists and biologists!



Verónica Miguel

Juan de la Cierva-Formación Postdoctoral Fellow, Immunobiology Lab, Spanish National Centre for Cardiovascular Research  (CNIC), Madrid, Spain
[email protected] | Personal website | Twitter

Could you discuss with us your postdoctoral work, summarize the main findings of your project presented during the 5th edition of the FEBS Fellow Meeting and explain why it is relevant to our field?

Chronic kidney disease (CKD) affects 10% of the population, and fibrosis driven by excessive accumulation of extracellular matrix (ECM) is the hallmark of CKD. Myofibroblasts are the key ECM-producing cells and are activated by cross-talk with injured proximal tubule and immune cells. Although a derangement in fatty acid oxidation (FAO) of the tubular epithelium is crucial in the pathophysiology of CKD, the metabolic rewiring of kidney myofibroblasts remains elusive.

During my postdoctoral training in the research group of Rafael Kramann at RWTH University Hospital (Aachen, Germany), we characterized the metabolic phenotype of myofibroblasts by using different experimental models: immortalized human cells, kidney organoids, mouse CKD models (aristolochic acid nephropathy and ischemia reperfusion injury) and kidney biopsies from CKD patients, in combination with Seahorse, SCENITH and single-cell gene expression technologies. We observed that activated myofibroblasts exhibit enhanced glycolysis and glutaminolysis whose inhibition reduces ECM production.

Could you tell us how the FEBS Long-Term Fellowship helped you during your postdoctoral stay?

After my PhD (Madrid, Spain), I was determined to incorporate single-cell RNA-sequencing technologies in my skillset. The FEBS Long-Term Fellowship was essential to join Kramann's lab, which has developed novel cutting-edge wet-lab and computational technologies for single-cell tracing in organ fibrosis. Its rich intellectual and technical environment provided me with the most suitable training both in terms of molecular tools, animal models and bioinformatics, but also the chance to expand my network connections and to apply for research funding, facilitating my transition towards research independence.

Could you share with us what are your long-term career goals and maybe explain what will be the next step for you in your career?

My long-term career goal is to establish my own research group to dissect the metabolic reprogramming heterogeneity and cellular cross-talk in organ fibrosis. Recently, I have joined the research group of David Sancho at CNIC (Madrid, Spain), where I am exploring the immune response associated with fibrogenesis. This will allow me to build my own academic profile at the crossroads of metabolism, immunology and single-cell transcriptomics.



Ana C. Queirós

FCT postdoctoral researcher, Champalimaud Foundation, Lisbon, Portugal
[email protected] | Personal website

Could you discuss with us your postdoctoral work, summarize the main findings of your project presented during the 5th edition of the FEBS Fellow Meeting and explain why it is relevant to our field?

Cell competition is a process through which weaker cells are recognized by their fitter neighbours and eliminated through apoptosis. Cancer cells exploit this mechanism to their benefit and become supercompetitive, in turn leading to the elimination of the normal cells which, in this scenario, become less fit. Understanding the mechanisms involved in this type of process may help to identify new therapeutic targets for cancer.

In my postdoctoral project in the group of Eduardo Moreno at Champalimaud Foundation (Lisbon, Portugal), I was able to optimize an in vitro cell competition assay that allowed me to study the transcriptional alterations occurring during cell competition in cancer cells of both winner and loser cells. We showed that loser cells are eliminated through caspase-dependent apoptosis and decrease proliferation and migration, whereas winner cells survive better, and proliferate and migrate more. Through conditioned media experiments we showed that secreted factors in the media are enough to induce the winner cell characteristics, but cell–cell contact is needed for the elimination of the loser cells. Through RNA-sequencing and other functional studies, we identified new important players involved in this process such as aquaporin-3 (AQP3). This gene is upregulated in the winner cells, and when silenced cell competition is no longer observed which, together with other published studies, suggests that AQP3 could be a new therapeutic target. 

Could you tell us how the FEBS Long-Term Fellowship helped you during your postdoctoral stay?

After my PhD (Barcelona, Spain), I decided to partly change the topic of my research and study the regulatory mechanisms occurring during cell competition in the context of cancer. The FEBS Long-Term Fellowship allowed me to join the Champalimaud Foundation in Lisbon and pursue this new and exciting topic, where I was able to deepen my knowledge in new molecular and cellular biology tools, as well as to improve other skills, such as grant writing. The FEBS Long-Term Fellowship also allowed me to strengthen my independence and develop a competitive profile to apply for other independent funding, which is playing a major role in my career development.

Could you share with us what are your long-term career goals and maybe explain what will be the next step for you in your career?

My goal is to become an independent group leader focused on understanding genomic regulatory networks occurring in the development and progression of specific hematologic cancers, to help identify new therapeutic targets and more efficient and less invasive diagnostic and prognostic tools. I have recently started a project on multiple myeloma, aiming at studying liquid biopsy alternatives to explore the (epi)genetics mechanisms associated with response and resistant to specific drug treatments.



Irma Querques

FEBS, EMBO and Branco Weiss Postdoctoral Fellow, Jinek Group, Department of Biochemistry, University of Zurich, Switzerland | Appointed Assistant Professor and Group Leader at the Max Perutz Labs, University of Vienna, Austria.
[email protected]; [email protected] | (New) lab website | Twitter

Could you discuss with us your postdoctoral work, summarize the main findings of your project presented during the 5th edition of the FEBS Fellow Meeting and explain why it is relevant to our field?

I have a long-standing interest in the molecular mechanisms by which transposable elements move within and between genomes and I strive to exploit these insights for the development of novel genome engineering tools. During my postdoctoral training in the research group of Martin Jinek at the University of Zurich, I have studied the mechanism of movement of CRISPR-associated transposons, the first natural RNA-guided DNA insertion machineries discovered to date. Our studies have made critical contributions to the molecular understanding of these systems, paving the way for their development as next-generation genetic tools that could be used to insert therapeutic genes at specific positions in the genome of human somatic cells.

For more information on my postdoctoral work supported by the FEBS Long-Term Fellowship, and my current and future research plans, please read our studies published in Nature and visit the website of my brand-new research lab.

Could you tell us how the FEBS Long-Term Fellowship helped you during your postdoctoral stay?

The FEBS Long-Term Fellowship supported my work on the high-risk/high-gain project focusing on CRISPR-associated transposons in the laboratory of Martin Jinek, a pioneer in the field of CRISPR and genome editing. Given my background on mobile genetic elements, my stay in the Jinek lab allowed me to gain complementary expertise in the CRISPR field and extensive training in state-of-the-art cryo-electron microscopy techniques, which will be a major future asset in my own research lab. As a recipient of FEBS, EMBO and Branco Weiss fellowships, I had the opportunity to be involved in the dynamic and vibrant worldwide network of current and former Fellows. This was pivotal to broaden my overall research vision and establish new collaborative projects and connections, while pursuing my scientific goals and taking my career steps towards independence.

Could you share with us what are your long-term career goals and maybe explain what will be the next step for you in your career?

My long-term career goal is to establish a multidisciplinary research program in my own team at the Max Perutz Labs, focusing on mechanistic and translational studies of mobile genetic elements. In the long run, we envision making key contributions to the mechanistic understanding and harnessing of mobile DNA in nature and technologies, with a long-term potential to address current challenges in the fields of genome editing, biotechnologies and biomedicine.



Pierre Santucci

CNRS Research Associate, Laboratoire d'Ingénierie des Systèmes Macromoléculaires (LISM), UMR7255-CNRS, Marseille, France
[email protected] | Personal websiteTwitter

Could you discuss with us your postdoctoral work, summarize the main findings of your project presented during the 5th edition of the FEBS Fellow Meeting and explain why it is relevant to our field?

To cure tuberculosis (TB), infected individuals need to have a daily chemotherapy with multiple antibiotics for at least 6 months. Such treatment is excessively long and often associated with numerous side effects, so developing new drug regimens that are shorter, less toxic and more efficient for TB patients is desperately needed. To help achieve this goal, it is essential to better understand the mode(s) of action of anti-TB drugs that are already available and provide molecular information that might further help to establish new therapeutic interventions.

During my postdoctoral training in the research group of Maximiliano Gutierrez at The Francis Crick Institute (London, UK) we developed new imaging modalities that allowed us to visualise and quantify antibiotic levels and mode of action within infected cells in a BSL-3 laboratory. Using such technology, we discovered that the front-line anti-TB drug pyrazinamide (PZA) requires acidic subcellular environments to display optimal accumulation and efficacy in cellulo and demonstrated that it essentially targets Mycobacterium tuberculosis intrabacterial pH homeostasis.

To know more about our work at The Francis Crick Institute, please visit our website or read our original studies supported by the FEBS Long-Term Fellowship, published in Nature Communications and in mBio.

Could you tell us how the FEBS Long-Term Fellowship helped you during your postdoctoral stay?

After my PhD (Marseille, France), I decided to expand my competences in microbiology with training in the latest state-of-the-art imaging technologies in the context of a relevant human pathogen. The FEBS Long-Term Fellowship played a key role in my young academic career by allowing me to join The Francis Crick Institute in London. Beyond the acquisition of complementary scientific knowledge, and the reinforcement of my skills on multiple levels, the FEBS Long-Term and Marie Skłodowska-Curie Individual Fellowships allowed me to gain independence through their financial support and build up a strong and competitive academic profile. It is indeed a crucial building block for any young scientist and clearly a major contributor in enhancing our potential and careers.

Could you share with us what are your long-term career goals and maybe explain what will be the next step for you in your career?

My long-term career goal is to establish my own research group to tackle important biological questions that may help the development of new drug regimens against infections. Recently appointed CNRS Principal Investigator in Marseille, I will develop my research topic aiming at investigating how mycobacterial pathogens adapt to fluctuating lung environments, with a special emphasis on nutrient stresses and antibiotic tolerance. Very exciting times!


Lorea Valcarcel-Jimenez

Juan de la Cierva Incorporacion Fellow-Research Associate at UPV/EHU, University of the Basque Country, Spain
[email protected]Twitter

 Could you discuss with us your postdoctoral work, summarize the main findings of your project presented during the 5th edition of the FEBS Fellow Meeting and explain why it is relevant to our field?

Fumarate hydratase (FH) is a mitochondrial enzyme that catalyses the hydration of fumarate to malate in the TCA (tricarboxylic acid) cycle. Germline mutations of this enzyme lead to HLRCC (hereditary leiomyomatosis and renal cell carcinoma), a cancer syndrome characterized by a highly aggressive form of renal cancer. Although HLRCC tumours metastasize rapidly, FH-deficient mice develop pre-malignant cysts in the kidney rather than carcinomas. Therefore, it was not known how tumorigenesis occurred in these tumours. During my postdoctoral work at Christian Frezza's lab (Cambridge, UK), we performed a genome-wide CRISPR/Cas9 screen that allowed us to identify the loss of the histone cell cycle regulator (HIRA) as a main oncogenic event in Fh1-deficient cells. HIRA loss enhanced proliferation and invasion in vitro and in vivo through the activation of the oncogene MYC. These results are instrumental for understanding the mechanisms of tumorigenesis in HLRCC and the development of targeted therapies for the patients.

If you want to know more about this and other work carried out during the fellowship, visit our publications at Science Advances and Nature Reviews Molecular Cell Biology.

Could you tell us how the FEBS Long-Term Fellowship helped you during your postdoctoral stay?

After my PhD (CICbiogune, Basque Country) I decided to work more deeply on metabolism and the role it plays during tumorigenesis and metastasis. The FEBS Long-Term Fellowship allowed me to join Christian Frezza's lab, a leader in cancer metabolism, at the MRC Cancer Unit at the University of Cambridge. Over 3 years, it allowed me to enhance my technical skills at several levels and establish new collaborations but, more importantly, it helped me to develop my independence as a young researcher to build a solid academic career.

Could you share with us what are your long-term career goals and maybe explain what will be the next step for you in your career?

The work carried out during my Fellowship allowed me to come back to the Basque Country as a Research Associate with a highly competitive grant (Juan de la Cierva Incorporacion). This new position will help me to develop my own research lines and will be crucial to apply for tenure track positions. My main aim will be to study how tumour cells interact with their microenvironment at multiple levels to metastasize. Gaining this knowledge, I hope to develop novel personalized therapies for cancer patients.



Guido van Mierlo

Marie Skłodowska-Curie Postdoctoral Fellow, Laboratory of Systems Biology and Genetics, Institute of Bio-engineering and Global Health Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland
[email protected] | Personal website | Twitter

Could you discuss with us your postdoctoral work, summarize the main findings of your project presented during the 5th edition of the FEBS Fellow Meeting and explain why it is relevant to our field?

Obesity is the leading preventable cause of death worldwide and over 15% of all adults are affected. Not every individual is equally prone to becoming overweight, and also not everyone who is overweight will become obese. Understanding how interindividual differences contribute to this process might aid in uncovering novel risk factors or rather targets for therapy. In my research in the laboratory of Bart Deplancke, we use high-throughput molecular profiling techniques including (epi)genetics and transcriptomics to assess the homeostasis of fat cells and their fat stem cell progenitors in a spectrum of normal weight to extreme overweight and obesity. We are at the centre of a large data collection endeavour, and currently we have almost finished the data collection phase and are already making good progress with the data analysis. Amongst others, we have observed some striking differences in the state and function of fat stem cells derived from overweight and obese individuals compared to those from human individuals with a normal weight. The dataset we created here provides a rich molecular resource that describes fat (stem) cells in the progression from a normal weight to overweight and consequently obesity.

Could you tell us how the FEBS Long-Term Fellowship helped you during your postdoctoral stay?

One of my goals after obtaining my PhD was to go abroad for a postdoc, during which I wanted to switch from more wet-lab research to computational biology. The FEBS Long-Term Fellowship gave me the exciting opportunity to go to the EPFL in Lausanne, Switzerland, and join a lab where the computational knowledge was strong. Going to a new lab with the funding provided by FEBS provided me with a lot of independence to advance my research skills and support further personal growth, allowing me to become a competitive interdisciplinary researcher with a solid basis in both experimental and computational approaches.

Could you share with us what are your long-term career goals and maybe explain what will be the next step for you in your career?

My long-term goal is to start my own research group, in which I aim to combine my experimental, mainly proteomics-oriented skillset, with my newly obtained computational expertise. The goal is to combine these skills to move towards translational research and focus on understanding the genetic basis of disease susceptibility. Several 'omics' approaches will be at the heart of this, and I am looking forward to the exciting challenges and opportunities this will bring.


 

Vera Wiersma

Postdoctoral Fellow, University of Zurich, Department of Quantitative Biomedicine, Switzerland
[email protected] | Lab website | Twitter

Could you discuss with us your postdoctoral work, summarize the main findings of your project presented during the 5th edition of the FEBS Fellow Meeting and explain why it is relevant to our field?

My postdoctoral research focuses on the neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), which share overlapping symptoms, genetic causes, neuropathological features and to date are both incurable. Specifically, I aim to understand the molecular mechanisms that force the essential RNA-binding protein TDP-43 to be incorporated in large insoluble inclusions that are found in neurons in the central nervous system of almost all ALS and about half of FTD patients. In the quest to unravel the molecular drivers of this TDP-43 dysregulation, I focus on liquid––liquid phase separation (LLPS), a process used by cells to dynamically concentrate TDP-43 and other proteins in membraneless liquid droplets. Albeit handy for the compartmentalization of cellular functions, these droplets may bear the risk of transitioning into irreversible solid inclusions. Using cultured human neural networks, I set out to identify the molecular players that drive TDP-43 LLPS in physiology and neuropathology. As part of this ongoing effort, the team recently uncovered that self-oligomerization of TDP-43 via its N-terminal domain governs its LLPS behaviour and modulates its aggregation pattern in neurons (for further reading, see Preprint). Detailed insight into physiological and aberrant TDP-43 LLPS is warranted to grasp the potential of LLPS as a molecular target in therapeutic approaches for ALS and FTD.

Could you tell us how the FEBS Long-Term Fellowship helped you during your postdoctoral stay?

The FEBS Long-Term Fellowship has been of key importance for my transition from a PhD student to postdoctoral fellow. After finishing my PhD at the VU University Amsterdam, the Netherlands in 2020, I was eager to continue my academic pathway in the field of molecular neurodegeneration. The FEBS Fellowship allowed me to join the Polymenidou laboratory at the University of Zurich, where I am expanding my scientific horizon every day in a highly collaborative and stimulating environment. The FEBS Fellowship kickstarted my academic career, created opportunities, gave me confidence and fuelled my motivation, all of which I am very grateful for. Meeting the other FEBS Fellows and seeing their great projects and scientific drive at the Fellows Meeting in Portugal this summer was truly inspiring and indeed it increased my enthusiasm even further.

Could you share with us what are your long-term career goals and maybe explain what will be the next step for you in your career?

I am currently diving deeper into the topic of ALS/FTD disease mechanisms as a postdoctoral fellow in the Polymenidou team, funded by the Dutch NWO Rubicon fellowship. My ultimate career goal is to establish my independent line of research in the discipline of neurodegeneration and work towards a progression-halting or curing therapy for these devastating disorders.


Thanks to Pierre Santucci for compiling answers following the FEBS Fellows Meeting.
Top image of post: 5th FEBS Fellows Meeting participants in Vimeiro, Portugal, 6–9 July 2022.

With the launch of the new FEBS Excellence Award scheme in 2021, the FEBS Long-Term Fellowships scheme closed to new applications. For current Fellowship types offered by FEBS, please see the FEBS website's Fellowships page.

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