© AG Simon, MDC
Simon Lab
Cell Biology of Immunity
Profile
Autophagy, the main cellular recycling pathway, plays a key role in keeping our Immune system young, functional and healthy. We study what autophagy degrades and provides to immune cells, as well as drugs or lifestyle changes that promote autophagy.
Cells are specialists in sustainability. They eat up all the organelles or larger molecular complexes that they no longer need – in order to then recycle the digestion products to build new structures. Autophagy is the name of this cellular recycling process, which yeast, but also all plant, animal and human cells use for themselves. Without autophagy, cells cannot develop and function normally, they age faster without it, and so does the immune system. In our lab we investigate the role of autophagy in the immune system and how to use autophagy to keep the immune system young.
© AG Simon, MDC
Team
Research
Autophagy is a major degradation pathway in the cell. While the ubiquitin/proteasome system degrades proteins, autophagy degrades bulk cytoplasmic material. Autophagosomes have been shown to engulf whole organelles, such as mitochondria, lipid droplets and ER and as a consequence autophagy impacts on metabolism, apoptosis, differentiation, cell cycle and cell fate decisions in the cell.
Over the last decade we have studied the role of autophagy in the development and function of hematopoietic and immune cells using in vivo models and in vitro techniques applied to human samples.
We pioneered a technique detecting autophagy in primary cells and showed a decrease in autophagy levels in ageing T lymphocytes (Phadwal et al, Autophagy 2012). Our research also revealed that red blood cells need autophagy to degrade mitochondria for their final maturation (Mortensen et al, PNAS 2010). Hematopoietic stem cells require autophagy for their maintenance (Mortensen, J Exp Med et al, 2011), and in the absence of autophagy, we observe a mild pre-leukemic phenotype. We measured low levels of autophagy in human acute myeloid leukemia samples (Watson et al, Cell Death Discovery 2015). Autophagy is required for neutrophil differentiation by providing free fatty (Riffelmacher et al, Immunity 2017). We also found that B2 cells require autophagy for self-renewal and their specific metabolism for survival, but not B1 cells (Clarke et al, JEM 2018). The survival/ maintenance of memory T cells is also reliant on autophagy. We find that inducing autophagy in T cells from aged donors with spermidine, an endogenous metabolite and polyamine, reverses an inefficient memory T cell response to influenza vaccination (Puleston et al, elife, 2014). Downstream of polyamines we have discovered a novel pathway that controls autophagy translationally, and is decreased with age. Re-introducing autophagy also improves B cell responses in older mice and adults. (Zhang et al, Mol Cell 2019, Alsaleh et al, elife 2020). Together these findings formed the basis for a clinical trial that aims at improving vaccine responses with polyamines with a particular focus on halting the waning of memory responses in older adults (https://clinicaltrials.gov/ct2/show/NCT05421546).
We are now trying to understand the role of autophagy in immune cell fate mechanistically, by identifying the autophagosomal cargo in vivo with a novel proximity labelling mouse model (Zhou et al, Nat Comms 2022). Furthermore we want to know whether and how autophagy in the microenvironment impacts on immune cells (Richter et al, biorxive 2022) and what autophagy provides to hematopoietic stem cells (Borsa, Obba et al. submitted). With this knowledge we are aiming to identify novel drug targets and drugs to be used for hematopoietic malignancies, in regenerative medicine and vaccination of older adults.
Publications
News
Jobs
2 three-year PhD candidate positions in Autophagy and Immunology
The Max Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Association is an international biomedical research center dedicated to understanding the molecular mechanisms of health and disease with the goal to devise new diagnostics and medicines. The MDC is a member of the Helmholtz Association, Germany's largest scientific organization, and offers an engaging research environment with cutting-edge research infrastructure. Currently, ~1250 employees and ~500 guest scientists work at the Berlin-Buch and Berlin-Mitte campuses. Our diverse workforce is a core strength that inspires creativity and innovation at the MDC.
The MDC is committed to improving human health through transformative biomedical research. Our goal is to pioneer discoveries for preventing, treating, and ultimately curing disease.
The Simon group seeks to uncover innovative strategies for extending healthspan.
Two PhD candidate positions (m/f/d) according to German pay grade 13, are available from now in the group of Anna Katharina (Katja) Simon at the Max-Delbrück-Center in Berlin in the area of ‘Autophagy in the immune system.’
Job Description
Our society is experiencing rapid aging due to lower birth rates and increased life expectancy. While people are living longer, the quality of life—particularly concerning health—has remained stagnant over the past 15 to 20 years. Elevated clinical frailty in older adults increases susceptibility to stressors such as falls, surgeries, and infections, highlighting the urgent need to improve the number of years spent free from significant disease burdens–also referred to as healthspan.
The Simon group studies the role of autophagy in fate, function and aging of immune cells, investigating immune metabolism, inflammation and immunity. Our work spans molecular and organismal levels, aiming to translate our findings into clinical trials. See Zhang et al, Mol Cell 2019, Alsaleh et al, Elife 2020, Zhou et al Nat Comms 2022, Borsa et al bioRxiv 2024, Piletic et al, bioRxiv 2024 for recent examples. We reviewed this field in Clarke et al, Nat Rev Immunology in 2018.
The MDC offers a highly vibrant scientific environment with state-of-the-art infrastructure for immunological platforms such as flow cytometry, single-cell transcriptomics, spatial transcriptomics, metabolomics and proteomics, imaging, and in vivo work. Numerous interactions with other groups working in immunology, metabolism, cell biology, and ‘OMICS’ on our Campus in Berlin-Buch are available.
We are seeking two PhD students to join the UNION project, which is funded by the European Union Marie Skłodowska-Curie Actions (MSCA). The Simon-led projects within the UNION program aim to tackle the decrease in autophagic function in immune cells of aging organisms, both in mice and humans, while evaluating their ability to improve vaccine responses in older adults. The Simon group, in collaboration with the UNION network, seeks to uncover innovative strategies for extending healthspan. Selected candidates will spend several months at partner laboratories within the UNION network, which includes sites in Germany and within the European continent. They will benefit from extensive expertise across various aging-related fields provided by the expert consortium of UNION. Participation in this network will maximize candidates’ future career prospects in science and beyond, as they will have opportunities for advanced training and networking environment, both at the MDC and through programs offered in the UNION network.
Requirements
The recruitment process will adhere to the principles outlined in the European Charter for Researchers.
We welcome applications from DCs of any nationality, gender, culture, religion, sexual orientation or age to undertake a PhD, fulfilling the following criteria:
1. Eligible candidates must not have a doctoral degree at the date of their recruitment. Researchers who have successfully defended their doctoral thesis but who have not yet formally been awarded the doctoral degree will not be considered eligible.
2. Comply with the mobility rule that eligible candidates must not have resided or carried out their main activity (work, studies, etc.) in Germany for more than 12 months in the 36 months immediately before their recruitment date (i.e. the starting date indicated in the employment contract/equivalent direct contract.
3. Eligible candidates must have a master’s degree relevant to the chosen position (including biology, medicine, biochemistry, bioinformatics or a related discipline, depending on each PhD project) or its equivalent that would entitle them to a doctorate one month before the labor contract starts, or must hold an official university qualification from a country of the European Higher Education Area with a minimum of 300 ECTs of official university studies.
4. Successful candidates must have a high level of proficiency in written and spoken English, which will be assessed with the motivation letter and the interview, respectively.
A female or minority candidate will be prioritized if two candidates are equally qualified.
Benefits
- international working environment with communication in English and German
- interesting career opportunities and a range of opportunities for further qualification and training
- Compatibility of family and career certified by the workandfamily audit (“berufundfamilie audit”)
- Support for "New Berliners" through the MDC Welcome & Family Office
You also benefit from:
- a remuneration in accordance with the collective agreement for the federal public service (TVöD-Bund), including additional company pension schemes
- a secure job
- flexible working hours and childcare support
- the possibility of mobile working
- an idyllic green campus, which is easily accessible by bicycle, public transport or car
- free use of Nextbike from the Buch S-Bahn station to the campus
- Subsidy for the job ticket as well as discounts in the campus canteen
- On-campus health and fitness center
- additional health benefits such as flu vaccination, eye test, ergonomics advice at the workplace
Further Information
https://www.mdc-berlin.de/simon
https://www.kennedy.ox.ac.uk/research/simon-group-autophagy-in-the-immune-system
