Grant reports

Snapshots from NAS Conference grant receivers

Reports from Conference grantees

Rubén Gómez Sánchez, PhD

EMBO workshop “Autophagy Across Scales”

23rd-27th September 2024, Sorrento, Italy

The EMBO Workshops on autophagy are well-recognized by the scientific quality and diversity in working models, which provides a great overview of the current state of the field. This year the EMBO Workshop was entitled Autophagy across scales, and held in Sorrento (Italy) on 23rd-27th September 2024. Along these 5 days, the program covered autophagy from every single angle, in which renowned researchers but also novel ones were providing valuable insights about autophagy, from the molecular mechanisms to the translational ones. I was fascinated about how autophagy is evolving into a more interdisciplinary field, where the combination of bioinformatics, biophysics, biochemistry and cell biology provides a new view of our research. In this regard, the location of the venue allowed me to network colleagues with different expertise and have fruitful discussions. Besides all the science-related topics, we had time to have a guided visit in Pompeii, where I was amazed walking through the Roman life and how this society lived 2,000 years ago. All this was possible by the full dedication of the meeting organizers (Sascha Martens, Antonella De Matteis and Helene Knaevelsrud) for preparing such a great conference.

My abstract entitled “The Phagophore-endoplasmic Reticulum Membrane Contact Sites are a Key Coordinator of Autophagosome Biogenesis” was selected for a short talk, having the chance to present our current study about the role and regulation of the membrane contact sites during the autophagosome generation. This gave me the opportunity to discuss our results with experts in this particular topic, but also to the rest of the experienced audience.

I would like to thanks Nordic Autophagy Society for the financial support through the NAS Conference Grant. My presence in this workshop has been essential to share our current project with the autophagy community, but also to help me in consolidating already-established collaborations and expanding my network for new ones.

Anastasia Knyazeva, PhD

EMBO workshop “Cell polarity and membrane dynamics”

21st-25th May 2023, Sant Feliu de Guíxols, Girona, Spain 

My name is Anastasia Knyazeva and I am a 4th year PhD student in Yaowen Wu lab, Umeå University, Sweden. I was participating in EMBO workshop “Cell polarity and membrane dynamics” which was held on 21-25 May 2023 in Sant Feliu de Guíxols, Girona, Spain. During my PhD project I am investigating novel non-canonical LC3 lipidation process, which is associated with recycling endosomes. Workshop was organized by an amazing team of researchers, and topics of presentations, keynote lectures were very diverse – from cell polarity and migration mechanisms in various model organisms and cell lines to membrane trafficking pathways accessed by cell biology and structural methods. Several presentation and posters were focused on canonical autophagy and mitophagy processes. For example, Sascha Martens from University of Vienna presented some outstanding findings in understanding of Atg2 protein machinery and novel pathways and players during the tuning of mitophagy. Overall, this conference gave me an opportunity to gain more knowledge about complex interconnection of different membrane trafficking processes in cells, and also how this knowledge can be applied to understand single-cell physiology, cell-cell communication and organs development.

I was selected to present a poster entitled “Dissecting ESCRT-III function in endosomal recycling by a chemical genetic approach”. During poster session I was lucky to have fruitful discussion with researchers from different fields, and that gave me opportunity to have novel views on my current research. It was pleasant to find another group at the conference, which is investigating the same IST1 protein, but in yeast model, and we independently found similar phenotypes in different models upon IST1 functions inhibition.

I appreciate Nordic Autophagy Society for providing me with the financial support for attending that fascinating EMBO workshop. This event became truly one of the most significant moments during my work as a PhD student.

Makoto Shimozawa, PhD

10th International Symposium on Autophagy

23rd – 27th October 2022, Sapporo, Japan

International Symposium on Autophagy (ISA) is one of the most prestigious international meetings in the autophagy research field, which was firstly organized by Nobel Prize laureate, Dr. Yoshinori Ohsumi. In ISA, worldwide top autophagy researchers present the latest research about basic molecular mechanism of autophagy as well as the role of autophagy in diseases.

ISA had seven sessions focusing on three different main topics: mechanism of autophagy, selective autophagy, and physiology & diseases. One of the key topics in the mechanism session was about the autophagy-related gene 9 (Atg9). Several researchers revealed the detailed function of Atg9 – Atg2 complex on autophagosome formation. Especially, Dr. Tooze analyzed molecular details of the Atg9 – Atg2 complex by using a structure modeling approach and revealed functional importance of this complex on lipid transfer to autophagosomes. The physiology & diseases sessions were the most exciting for me because I am working on the role of autophagy in Alzheimer’s disease (AD). Dr. Cuervo showed their groundbreaking research about chaperone mediated autophagy (CMA). They established a neuronal-specific CMA deficient mouse model which showed impaired motor coordination and accumulation of tau aggregation, suggesting the importance of functional CMA to prevent age-related diseases including AD. I presented my research titled “Autophagy impairment liked with synaptic dysfunction in hippocampus of App knock-in Alzheimer mouse models” in the poster session. We revealed that autophagy deficiency is linked to synaptic disfunction in App knock-in mouse models by using RNA-sequencing, immunofluorescence staining, electron microscopy, and SV2A-PET.

The ISA is one of the best conferences which I have attended. It had a good atmosphere to discuss about autophagic research with legendary researchers as well as young researchers. I look forward the 11th ISA at Melbourne, Australia.

I would like to thank the NAS for supporting my attendance at the 10th ISA at Sapporo. Thanks to your support, I had a valuable experience and got new ideas and possible collaborations from presentations and discussions.

Karolina Pircs, Postdoc

EMBO Autophagy: From molecular principles to human diseases

26th – 30th August 2019, Crieff, Scotland, UK

EMBO Autophagy conference is held every second year. This is the biggest and most relevant autophagy conference held in Europe, which is uniting various labs with >500 participants working with autophagy all over the world. It is foremost the best conference to attend in autophagy to keep up with the current state of the field and to stay in contact with all relevant autophagy scientists. The aim of this EMBO meeting was to integrate diverse perspectives on the function of autophagy from the fields of genetics, cell biology, oncology, immunity, metabolism, neurodegeneration and drug discovery.

The specific research topic created a very focused and well-organized meeting with superior venue and services. The conference was 5 days long giving time for fruitful discussions and also special social events. These events created a great atmosphere to network and get to know each other better. I presented my first authorship study as a poster, which is close to submission. This was a great opportunity for me to get feedback and some hints and tips for the paper submission. The meeting greatly expanded my network for future collaborations.

It was without a doubt a great, enriching experience to attend this meeting in Crieff and I am very grateful for the opportunity that NAS awarded me with this travel grant.

Marisa Di Monaco, PhD

EMBO Autophagy: From molecular principles to human diseases

26th – 30th August 2019, Crieff, Scotland, UK

As a NAS Member I received funding to attend the EMBO Workshop entitled “Autophagy: Molecular Principles to Human Disease” held in Crieff, Scotland, United Kingdom, on 26-30th August 2019. I applied to the conference with the desire to present my current PhD research project; which involves characterising molecular mechanisms which drive the induction of autophagy in the nucleus, through identification and characterisation of novel LC3-interacting region (LIR) containing proteins.

The aim of this EMBO Workshop was to integrate diverse perspectives on the function of autophagy from a wide range of fields including genetics and cell biology. After submitting an abstract entitled “Self-regulation of autophagy genes by Atg8a and its interacting partners YL-1, Sequoia, Sir2 and DOR in Drosophila”, I was delighted to find out I had been selected to deliver a talk at the workshop. As a final year PhD student, this was a fantastic opportunity for me to gain invaluable experience in delivering my work to an experienced audience, as well as allowing me to discuss my future work plans with a wide range of academics.

The conference line-up was excellent with talks from across the field being delivered from academics such as Sharon Tooze, Vojo Deretic and Claudine Kraft, just to name a few. Each of the sessions which made up the days of the conference were themed so that the stories being told chronologically across the field; with session 1 entitled The beginning: forming autophagosomes” and the final session: “Autophagy in metabolism and therapy.” In particular, it was of great interest to me to have an insight into the growth of translational autophagy being conducted at an international scale.

Attending this workshop allowed me to be exposed to, and network with, established scientists, clinicians and industry. I am extremely motivated to continue my research career in autophagy after I complete my PhD next year, so I would like to thank the NAS Grant Committee for supplying me with the funds to attend this workshop, further inspiring and motivating me as a research scientist.

Reports from Lab exchange grantees

One of the aims of the Nordic Autophagy Society (NAS) is to promote excellent research in the autophagy field. To achieve this goal, the NAS offer NAS Lab Exchange Grants (https://nordicautophagy.org/lab-exchange-grants/), giving the opportunity for a research stay in another group in a period from 5 to 90 days. These research exchanges allow the application of methodologies which are not available in the NAS member’s laboratory, and eventually they will facilitate valuable collaborations between research groups.

Christina Sveen

Evaluating the expression of fibroblast activation protein in cancer cells and cancer-associated fibroblasts for selective targeting of fibroblast autophagy

Host: Prof. Ingrid De Meester (University of Antwerp, Belgium) 

Duration of visit: 2 weeks (February 4th to February 16th, 2024)

It has been reported that the growth of cancer cells may be affected non-cell autonomously by autophagic processes in cancer-associated fibroblasts (CAF) in the tumor microenvironment. The aim of the project related to this lab exchange is to selectively target autophagy in CAFs with novel drug conjugates of autophagy modulators attached to a CAF-specific binding moiety, which exploits the fact that CAFs frequently express high levels of fibroblast activating protein (FAP) on their cell surface. Before moving forward with this project we needed to assess the expression of FAP in our cancer cell lines and CAFs. During my lab exchange at the University of Antwerp, I learned how to detect FAP by performing western blotting, utilizing both fluorescent and chemiluminescent detection methods, and by confocal microscopy. During my stay, I got well acquainted with the methods, and already obtained promising results, indicating that the CAFs express substantial amounts of FAP compared to negligible expression in the cancer cells. This could allow selective targeting of CAFs over cancer cells based on FAP expression.

In addition to the interesting and successful results, the valuable learning experiences I obtained during my visit in De Meesters lab will allow me to establish appropriate assays to investigate FAP expression in our lab in Oslo. My time in Antwerp has been very educational, and I have had 2 great weeks thanks to all members in the De Meester lab. A special warm thanks to Yentl Van Rymenant for her so kind and always pleasant training and help before and during the whole stay. I would also like to say thank you to NAS for giving me this opportunity.

Apsana Lamsal 

Does arginine starvation induce selective or bulk autophagy?

Host: Dr. Nikolai Engedal (Oslo University Hospital)

Duration of visit: 4 weeks (Nov 22nd to Dec 17th, 2021)

Cancer cells can alter the Tumor Microenvironment by several mechanisms. They can have altered metabolism and recruit immunosuppressive cells, such as myeloid derived suppressor cells (MDSCs) or neutrophil-like cells, which can secrete arginase-1 (ARG1). We had observed a close link between ARG1 expression and reduced arginine in breast cancer tumors. We therefore hypothesized that local arginine depletion induces autophagy in the tumor. We observed arginine starvation was a strong signal for induction of selective autophagy receptors in breast cancer cells. So, we wanted to know if arginine starvation induces selective or bulk autophagy. To understand this, a lab visit to Dr. Nikolai Engedal’s group was arranged for measuring cytosolic cargo sequestration using the Lactate Dehydrogenase Sequestration (LDH) Assay. This assay allows quantitative measurement of autophagic sequestration of the endogenous cytosolic cargo protein lactate dehydrogenase. The assay was used with success during my stay and already provided some interesting results. In collaboration with Dr Engedal’s lab, we also made mKeima-based reporter cell lines. This further allows us to understand if arginine starvation induces only bulk autophagy, or also selective autophagy of mitochondria. From the very first day to the last, I had a pleasant lab visit with a very good lab environment and the visit was a great success. We will maintain an active collaboration with Dr. Nikolai Engedal. I thank NAS for providing me this opportunity.

Florentina Negoita

The role of SIK2 in autophagy and its link to human adipose tissue dysfunction in the development of type 2 diabetes

Host: Pr. Eeva-Liisa Eskelinen (University of Turku, Finland)

Duration of visit: 2 weeks (September 30 – October 11, 2019)

The aim of this project is to characterize the molecular mechanisms underlying the regulation of autophagy by SIK2 in adipocytes. Transmission electron microscopy (TEM) is currently considered to be the gold standard test for the evaluation of autophagy, but identification of autophagic structures is challenging, without proper expertise, and might lead to false conclusions. Thus, in order to learn how to correctly identify and differentiate autophagic structures from other cellular structures and how to quantify the TEM images, a research visit was organized in the lab of Pr Eeva-Liisa Eskelinen, a leading scientist on TEM imaging of autophagic structures. Adipocytes treated with a SIK inhibitor were imaged and images were then analyzed. We found a marked change in the number and volume of autolysosomes, in line with our previous data. With the protocol for TEM sample processing obtained through this collaboration, we are now planning to further explore our findings by establishing the TEM method in our own laboratory, and applying it to 3T3-L1 adipocytes treated with SIK2 siRNA. We will maintain an active collaboration with Pr Eeva-Liisa Eskelinen. In conclusion, the research visit was very successful. I received excellent training in TEM analysis of autophagic structures, and we also generated novel, interesting data, which has opened up a new direction of study in the project.

Pauline Verlhac

WIPIng out Flu: Role of WIPI2 in restricting Influenza A virus

Host: Prof. Jörn Dengjel (University of Fribourg, Switzerland)

Duration of visit: 7 days (June 16th-23rd 2019)

The ultimate goal of the project is to decipher how WIPI2 controls viral replication, using influenza A virus (IAV) as a relevant clinical model. Therefore, we plan to use an unbiased and broad approach to identify potential WIPI2 binding partners involved in the control of IAV infection. To do so, we have used stable isotope labelling by amino acids in cell culture (SILAC)-based quantitative mass spectrometry (MS) with proximity-dependent biotin labelling by fusing WIPI2 with APEX2 in order to identify interacting proteins in both infected and non-infected cells. To determine which WIPI2 neighbours are regulated by IAV infection, we combined APEX2 with SILAC-based MS. Neighbours identified thanks to this Lab Exchange will now be tested for their impact on IAV replication by siRNA interference and their interaction with WIPI2 confirmed by IP. The work was realised with the help of Devanarayanan Siva Sankar, who taught the experimental part, and Professor Jörn Dengjel for the statistical data analysis. The exchange allowed me to implement a new and innovative technique into our laboratory as well as to strengthen the collaboration between our two laboratories.

Yanyah Aman

Is mitophagy protective against tau aggregation in Alzheimer’s disease?

Host: Dr. William A. McEwan (University of Cambridge, United Kingdom)

Duration of visit: One month (May 6th to June 7th 2019)

Mitochondrial quality is tightly regulated by mitophagy, in which damaged mitochondria are degraded and recycled. However, the underlying mechanism remains elusive. We wished to investigate how mitophagy inhibits p-tau using a novel in-vitro system. For this purpose, an overseas visit to Dr McEwan’s lab was arranged in order to acquire and apply high-content quantitative assays for measuring cytosolic tau aggregation in situ. This assay not only allows to assess the impact of mitophagy inducers on the development of p-tau aggregates; but also provide a platform to evaluate whether mitophagy can aid in degradation of already established tau aggregates, which further enhances the translational relevance. The assay was used with success during my stay and already provided some interesting results. In collaboration with Dr McEwan’s lab, we will further explore on the underlying molecular mechanisms that contribute to p-tau pathogenesis with the perspective of the mitophagy and its role using this exciting seeded aggregation of tau model system.