Why should we care about lysosomes?
Lysosomes are the recycling centers in our cells, capable of breaking down all types of biological material. Multiple degradation pathways bring cargo to lysosomes, which are illustrated in the figure below. Autophagy (cellular self-digestion by lysosomes) is activated in response to starvation in all eukaryotic cells, and ensures survival by recycling dispensable cellular constituents for re-use in synthetic processes. In animals, autophagy has been adopted to serve additional functions beyond starvation survival that include regulation of lifespan, stress responses, cellular homeostasis, cell death, immunity, cancer, neurodegeneration diseases, obesity and lipid metabolism, and more. The biomedical relevance of autophagy is well-established by now, also evident from the 2016 Nobel Prize awarded to a yeast autophagy researcher. Phagocytic and endocytic breakdown pathways deliver extracellular cargo (such as bacteria/dead cell fragments and signaling ligands, respectively, along with their plasma membrane receptors) to lysosomes. LAP (LC3-associated phagocytosis) is a specialized phagosome maturation route that utilizes a subset of autophagy proteins independent of autophagosomes to promote lysosomal fusions. Lastly, crinophagy ensures continuous turnover of secretory granules, which can also be developmentally induced.
The various vesicular degradation pathways that bring cargo to lysosomes for recycling. Modified from the textbook: Molecular Biology of the Cell.
Annual news from the lab
Brief summaries of lab news are presented below for each year, starting from 2009. Here are a couple of links to list of our papers, PhD graduations etc, which you can check on for the latest info if you like:
MTMT Hungarian publication database
2024
This year brings our first research papers focusing on cultured human cells, without including any Drosophila data. First, we show that PI4P is key for bringing Syntaxin 17 to maturing autophagosomes to enable lysosomal fusion (published in Autophagy in another big rush because Noboru Mizushima's related story appears as preprint at Elife). Second, we characterize how lysosomes are activated by incoming cargo via TRPML1, releasing calcium ions from lysosomes during vesicle fusion (paper published in JBC). Arindam (co-first author in both papers) returns to India to set up his Ramanujan-funded group at Agharkar Research Institute. Dalma and Hussein defend their PhD theses. Judit Biro joins us, bringing her experience in Drosophila behavior assays.
2023
We manage to publish our story on how a special phagosome maturation program (LAP) in glia keeps the fly nervous system clean of debris to promote survival after traumatic brain injury. 6 years of work from Aron culminated in a Nature Comm paper! Gabor can finally give up his own research group in Budapest (staying to teach and mentor as part-time full professor), after successfully bridging the time between his move to a full-time group leader position in Szeged until his former colleagues establish their own groups in Budapest. Gabor wins his second Advanced Momentum grant, securing reasonable funding for the next 5 years. Gabor and Aron spend a 3-month sabbatical with Robin Hiesinger in Berlin to explore additional roles of glial phagocytosis in the Drosophila brain (funded by an EMBO Advanced Collaboration Grant).
2022
Adel defends her PhD thesis from work she did with Arindam on p62 LIR-disrupting CRISPR mutant flies - published this year in Autophagy because we get scooped by a mouse paper that had a similar message: autophagic turnover of ubiquitinated proteins is dispensable, partly because it gets compensated by antioxidant responses. Gabor manages to organize this years' EMBO Autophagy workshop in Eger, Hungary in June despite serious challenges: every COVID-postponed meeting takes place at this time (e.g., Gabor is speaking and chairing a session at the first EMBO Neuronal Autophagy meeting in May), flight disturbances, etc. Peti Lorincz wins a Momentum Starting grant, and Szabi is back from Norway, setting up their groups in Budapest and taking over the people, equipment, and reagents from Gabor's "heritage".
2021
We close several long-running projects with papers this year: lipidomics of autophagic membranes (Hajni), fly Atg8a and Atg8b (Andris), and Rab18 (Szabi). Saci and Attila defend their PhD theses in Budapest, Viki and Andris do the same in Szeged. Gabor Csordas returns from Germany to join us as another experienced postdoc in Szeged.
2020
This year brings lockdowns: our people are sitting at home for most of the year as COVID waves hit. Ironically, this year brought our best funding ever, and progress is disappointing because lab work is mostly not feasible. We manage to publish the first research paper that was fully done in Szeged: our Atg9 story of the fly ovary in Cell Death Differ.
2019
Peti manages to publish another Elife paper on Vps8/CORVET. Gabor gives up on doing experiments (for now) and dismantles his home fly pushing station. We win another Hungarian excellence grant called Leading Edge (Elvonal). Gabor is trusted at the Autophagy EMBO workshop in Scotland with the organization of the next meeting in this series.
2018
Our first crinophagy paper is published in J Cell Biol, describing the first animal model (Drosophila salivary gland) and identification of the first secretory granule-lysosome fusion factors. We publish our ykt6 story: a SNARE that is difficult to fit into the known model of autophagosome-lysosome fusion. After this, Szabi moves on for a postdoc in Norway. Gabor keeps giving talks at various meetings (not listed from now on). Hajni Laczko-Dobos, Arindam Bhattacharjee, and Aron Szabo join the Szeged lab as experienced postdocs.
2017
We manage to publish our Rab2 story in J Cell Biol, again in a big rush with others. Peti Lorincz and Saci Toth do most of the work and share co-first authorships. Kata defends her PhD. While we continue to publish from Budapest, some projects finally start to shape in Szeged. Gabor gives talks at the 8th International Symposium on Autophagy, Japan and at the 9th Physiology and Disease Symposium in Singapore.
2016
Running 2 labs (in Budapest and Szeged) works okay for now. Peti successfully develops the Drosophila larval nephrocyte model to delve into the roles of a vesicle tethering complex called CORVET, which shares 4 subunits with HOPS. His paper is published in Elife, where Randy Schekman oversaw the publication process as Senior Editor, Handling Editor, and one of the Reviewers. This is also the first year to publish more than 10 papers (6 with Gabor's senior authorship). Gabor gets an unfunded A for his ERC CoG proposal, and Wellcome Trust funding runs out in Budapest. He obtains his DSc (from the Hungarian Academy of Science) and habilitation (from Eotvos Lorand University) degrees. Gabor gives a talk at the Autophagy Keystone Symposium (and misses his chance to hike the Canadian Rockies due to recent ACL replacement surgery), and he organizes the annual JEDI meeting in Visegrad, Hungary.
2015
Our second group starts at the Biological Research Center in Szeged. First, Tomi Maruzs is overseeing renovations while finishing his PhD in the Sass lab. Later this year, Szilvi Bozso (technician), Zsofi Vecsei (postdoc), Kata Varga, Viki Kiss and Andris Jipa (PhD students) join us in Szeged, while Manuela and Szabi defend their PhD theses in Budapest. Gabor gives talks as invited speaker at the FEBS Congress, Germany, at this year's International Symposium on Autophagy, China, and at the 5th Junior European Drosophila Investigators (JEDI) meeting.
2014
This year brought the winning of a Hungarian excellence grant called Momentum (Lendulet). This Momentum Advanced grant funding will enable Gabor to start a second lab at the Biological Research Center in Szeged, the capital of Drosophila research in Hungary. We publish the role of HOPS tethering complex in autopohagosome-lysosome fusion, which we coordinate with Noboru Mizushima: the 2 papers appear in the same issue of MBoC. Peti Lorincz joins our group in a postdoc status after publishing his first author paper with Miklos Sass that will be needed to defend his PhD.
2013
We manage to publish in fancier journals this year: our discovery of the autophagosomal SNARE Syntaxin 17 and its role in normal fly lifespan and climbing appears in J Cell Biol, in a big rush because Noboru Mizushima's lab also identified Syntaxin 17's similar role in cultured human cells. Szabi's perseverence to find the autophagosomal SNAREs turned out quite nice! Pepe also followed his interest in cancer to show the role of the transciption factor Myc in autophagy: his paper got in at PLOS Genetics. Pepe and Agi (from her studies on the links between the proteasome and autophagy) defend their PhD theses.
2012
We publish the first research papers from our lab: one is about p62-based autophagy flux assays, and the other one is on transcriptional changes during autophagy and the role of Rack1. Thanks to these, Karolina and Balazs defend their PhD theses by the end of this year.
2011
We have finished the first screen, in the end testing close to 10,000 RNAi lines from multiple stock centers. Our 3 MSc students graduate, and Manuela and Szabi continue as PhD students with us. Balazs leaves to join the stainer team in Barry Dickson's lab in Vienna. Kriszta (and for half a year, Zsolt) join us as postdocs, which brings the birth of our cell culture work.
2010
We start the genome-wide RNAi screen in mosaic fat tissue of starved Drosophila larvae. One of our PhD students is taking a train to Vienna every other week, to bring 400 stocks to test in 2 weeks. We also carry out a microarray analysis of starvation responses in Drosophila larvae, and Balazs is trying to characterize some interesting genes that show transcriptional regulation.
2009
Our group has been established this year at Eotvos Lorand University, thanks to a generous Wellcome Trust startup grant. Gabor is fulfilling the roles of group leader, lab manager and postdoc, working along with an experienced technician (Sari Palfia), 3 diploma (Manuela Karpati, Szabi Takats, Dori Szendrei) and 4 PhD (Karolina Pircs, Agi Varga, Pepe Nagy, Balazs Erdi) students.