Skip to main content

Main menu

  • Home
  • Current issue
  • Past issues
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Peer reviewer login
  • Journal club
  • Alerts
  • Subscriptions
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

User menu

  • Log in
  • Subscribe
  • Contact Us
  • My Cart

Search

  • Advanced search
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

Login

European Respiratory Society

Advanced Search

  • Home
  • Current issue
  • Past issues
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Peer reviewer login
  • Journal club
  • Alerts
  • Subscriptions

Early Career Members at the ERS Lung Science Conference 2020: metabolic alterations in lung ageing and disease

Patricia P. Ogger, Johnatas Dutra Silva, Mahyar Aghapour, Irma Mahmutovic Persson, Christy Tulen, Renata Jurkowska, Niki D. Ubags
Breathe 2020 16: 200063; DOI: 10.1183/20734735.0063-2020
Patricia P. Ogger
1National Heart and Lung Institute, Imperial College London, London, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Johnatas Dutra Silva
2Wellcome–Wolfson Centre for Experimental Medicine, School of Medicine, Dentistry, and Biomedical Sciences, Queen's University Belfast, Belfast, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mahyar Aghapour
3Infection Immunology Group, Institute of Medical Microbiology, Infection Control and Prevention, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University, Magdeburg, Germany
4Immune Regulation Group, Helmholtz Center for Infection Research, Braunschweig, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Irma Mahmutovic Persson
5Institution of Medical Radiation Physics, Dept of Translational Medicine, Lund University, Malmö, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Irma Mahmutovic Persson
Christy Tulen
6School of Nutrition and Translational Research in Metabolism (NUTRIM), Dept of Pharmacology and Toxicology, Maastricht University Medical Center+, Maastricht, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Renata Jurkowska
7School of Biosciences, Cardiff University, Cardiff, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Niki D. Ubags
8Faculty of Biology and Medicine, University of Lausanne, Service de Pneumologie, CHUV, Epalinges, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: Niki.ubags@chuv.ch
  • Article
  • Info & Metrics
  • PDF
Loading

Abstract

The Lung Science Conference 2020 brought together leading experts in the field to discuss the latest cutting-edge science, as well as various career development opportunities for early career members https://bit.ly/2XZ5YGQ

Every year, the European Respiratory Society (ERS) organises the Lung Science Conference (LSC) in Estoril, Portugal, to discuss basic and translational science. The topic of the LSC 2020 was “Metabolic alterations in lung ageing and disease”. In addition to an outstanding scientific programme, the LSC provides excellent opportunities for career development and inclusion of Early Career Members (ECMs). All scientific and poster sessions are chaired by an ECM who is paired with a senior faculty member to allow ECMs to become acquainted with session chairing. In addition, 40 travel bursaries are made available to abstract authors and all bursary recipients are invited to take part in a mentorship lunch. Moreover, there is a session organised by the Early Career Members Committee (ECMC) dedicated to career development. Here, we describe the scientific highlights of LSC 2020 for those who could not attend.

The ERS presents several awards at the LSC and here we will highlight all winners of the LSC 2020 awards. The five highest ranked abstracts from ECMs are presented during the Young investigator session. Patricia Ogger (UK) was presented with the William MacNee Award for the best presentation in this session. Several abstracts were selected for programmed oral presentations and Renata Jurkowska (UK) was presented with the inaugural Geoffrey Laurent Award for the best oral presentation. Moreover, the organisers presented eight Distinguished Poster awards to Anne-Sophie Lamort (Germany), Julia Frankenberg Garcia (UK), Johnatas Silva (UK), Pauline Esteves (France), Claudio Bussi (UK), Elodie Picard (France), Felix Ritzmann (Germany) and Alen Faiz (Australia) for their excellent contributions during the poster session.

Opening lecture

The introduction and opening lecture was given by Luke O'Neill (Dublin, Ireland). He introduced the term “immunometabolism” [1] and discussed its potential importance in drug efficacy. Prof. O'Neill mentioned that many drugs, although very promising in pre-clinical stages, were not proven to be efficient in clinical trials. This may be because although the immunology and pathology was studied and targeted, the influence of the metabolism was understudied. To move the field forward, these effects and metabolic mechanisms need to be further studied in order to “boost efficacy” of drugs, and ultimately be able to more effectively treat lung diseases such as asthma and chronic obstructive pulmonary disease (COPD). He further discussed the role of cell death, particularly how caspases and inflammasomes can affect homeostasis, being potential targets for improvement of drugs and patient response.

The nucleotide-binding domain leucine-rich-containing family pyrin domain-containing-3 (NLRP3) inflammasome is a sensor for metabolic disturbance and that is why the NLRP3 inhibitor MCC950 (also called diarylsulfonylurea cytokine release inhibitory drug (CRID3)) was considered as a “game changer” [2]. Recent studies have specified the mechanisms of CRID3, indicating that inhibitory effects are exerted via the NAIP, CIITA, HET-E and TP1 domain with NTPase activity (NACHT) of NLRP3 [3], and reduce inflammation in murine airway and skin inflammatory disease models [4, 5].

Caspases play a role in inflammatory diseases and caspase-11 has been shown to promote allergic airway inflammation [6]. When performing studies in caspase-11 knockout mice, there is reduced tissue inflammation by histology, decreased total cell counts from bronchoalveolar lavage fluid and, importantly, eosinophil reduction in the knockout animals. Caspase-11 corresponds to caspase-4/5 in humans. Analysis of sputum samples from asthma patients revealed increased caspase-4 levels, as well as elevated levels of NLRP3, caspase-1, caspase-5 and interleukin (IL)-1β [7].

The Warburg effect was first described by Otto Warburg in the context of cancer, observing that cancer cells use glycolysis as their main metabolic pathway, even in the absence of hypoxia. In his talk, Prof. O'Neill highlighted the importance of metabolism for cell function and as a driver of disease, and showed studies linking glucose levels in the lungs to areas of fibrotic foci in patients with idiopathic pulmonary fibrosis (IPF) [8]. Fibrosis is considered to result from dysregulated wound healing and no cure is currently available. New drugs, such as pirfenidone and nintedanib, slow disease progression but a better understanding of the disease is urgently needed. Investigating cell metabolism in the context of pulmonary fibrosis could offer new therapeutic opportunities, as clinical studies [9–11] and pre-clinical fibrosis models [12] indicate a dependence of fibrotic foci on glucose and glycolysis.

Pyruvate kinase M2 has been shown to activate Warburg metabolism in M2 macrophages and is therefore a critical determinant in inflammatory responses [13]. In this opening lecture, Prof. O'Neill emphasised the importance of the Krebs cycle and the products it generates, one of them being itaconate. Besides antibacterial functions, itaconate has recently been shown to limit NLPR3-dependent cytokine release, such as that of IL-1β from peripheral blood mononuclear cells in patients with cryopyrin-associated autoinflammatory syndromes. When lipopolysaccharide and itaconate were administered at the same time, an improved survival rate was observed [14, 15].

The main and important message from Prof. O'Neill was that “metabolism is the driver (of disease) while genes are the passengers”. With this statement, he pointed towards the fact that diseases increasing over the past decades have not emerged due to genetic variation, while environmental exposure stimuli, diet and behaviour have drastically changed – and so has metabolism. Metabolism is poised to sense these modifications and thus, in turn, drives changes in gene expression that are causing disease or imbalance of health status. Therefore, understanding the underlying metabolic changes may improve therapeutic targets in the future [16].

Immunometabolism and inflammageing

Craig Wheelock (Stockholm, Sweden) kicked of the first session by discussing the metabolic profiling of severe asthma, and its implications for disease phenotyping and treatment. Metabolomic analysis provides an integrative molecular signature of the genome, transcriptome and proteome, which ultimately can be linked to a disease phenotype. Urinary eicosanoids have been demonstrated to identify molecular phenotypes of asthma and eicosanoids may be important components that aid in our understanding of the biochemical processes that drive asthma severity.

Thereafter, Annika Karger (Bad Nauheim, Germany) discussed how the long coding RNA ADPGK-AS1 can control antitumour immunity in macrophages via metabolic reprogramming. She concluded that enhanced understanding and potential targeting of this long coding RNA could have the potential to serve as a future therapeutic approach in lung cancer treatment.

Next, Rajkumar Savai (Bad Nauheim, Germany) reviewed the impact of metabolic reprogramming of tumour-associated macrophages on lung cancer progression. He discussed the use of a variety of novel high-resolution small animal in vivo imaging techniques to gain insight into tumour evolution and progression. Furthermore, he provided an exciting set of data describing the potential to reprogram tumour-associated macrophages towards antitumour responses [17].

The last presenter of the first session, Carol Liang (Los Angeles, CA, USA), showed a reduction in the number and repair capacity of type II alveolar epithelial cells (AECII) in the lung of both ageing and IPF experimental mouse models using single-cell sequencing. Furthermore, she showed that zinc transporter 8 levels are attenuated in the AECII of these models, suggesting deficient zinc metabolism as a shared mechanism in ageing and IPF. Exogenous zinc treatment was able to replenish AECII differentiation in the lungs of IPF patients but not in ageing mice.

Mitochondrial dysfunction in lung ageing and disease

Recent literature suggests a key role for mitochondrial dysfunction in lung ageing, and pathogenesis of lung diseases such as COPD and asthma [18, 19]. Emerging evidence shows that mitochondria are implicated in the regulation of critical cellular processes of cells of the airways such as inflammation, oxidative stress and cell death pathways, alongside their traditional role as the powerhouse of the cell [19, 20]. That is why the focus of this second session was on mitochondrial dysfunction in lung ageing and disease.

Matt Whiteman (Exeter, UK) opened this session by describing that mitochondrion-targeted hydrogen sulfide (H2S) suppresses and reverses cigarette smoke-induced inflammasome activity and lung injury in experimental COPD, and showed results of an in vivo animal smoke exposure study. This research built further on previous findings suggesting a central role for H2S in the development of COPD and one of the key processes involved in COPD pathogenesis, i.e. inflammation, which appointed H2S as a potential therapeutic target [21, 22].

The next talk focussed on the development of asthma, in which the role of mitochondrial (dys)function is increasingly gaining attention. As airway remodelling, i.e. airway smooth muscle hypertrophy and hyperplasia, is a crucial hallmark involved in the pathogenesis of asthma [23], Thomas Trian (Bordeaux, France) discussed mitochondria located in airway smooth muscle as a driver of airway hyperresponsiveness in asthma. Elevated mitochondrial mass, increased abundance of key regulators of mitochondrial biogenesis, elevated carnitine palmitoyltransferase 2 protein levels and upregulation of oxidative phosphorylation were shown in in vitro studies investigating airway smooth muscle cells of asthma patients.

Thereafter, an ECM, Thomas Meul (Munich, Germany), demonstrated that mitochondrial metabolism is a regulator of cellular proteostasis in a short oral presentation. In mitochondrial DNA-mutated mice, accumulation of NADH, and decreased levels of protein synthesis and degradation were observed. Resupplying those mice with aspartate, an important regulator of the malate–aspartate shuttle involved in translocation of electrons over the mitochondrial inner membrane, reactivated the metabolic system (i.e. shift from oxidative phosphorylation to glycolysis) and rescued proteostasis.

In the second part of the session, Suzanne Cloonan (Dublin, Ireland) discussed the role of mitochondrial iron in the susceptibility to, and pathogenesis and progression of COPD. Besides impairment of the immunometabolism of alveolar macrophages of smokers and COPD patients [24], and the involvement of ferroptosis in COPD development, she discussed the central role of iron-associated mitochondrial dysfunction in the pathogeneses of COPD. This was illustrated by a study in which her group showed that preventing cigarette smoke-induced mitochondrial dysfunction in the structural cells of the airways of mice (e.g. iron regulatory protein 2-deficient mice, mice treated with a mitochondrial iron chelator or mice fed a low-iron diet) protected against the development of emphysema and bronchitis [25]. This presentation further highlighted the causal role that mitochondria, particularly mitochondrial iron, play in the development of COPD.

Next, Christy Tulen (Maastricht, the Netherlands) focussed on the effect of cigarette smoke exposure on the molecular regulation of mitochondrial metabolism in human bronchial and AECs. She showed that key regulators of mitochondrial metabolism, mitochondrial biogenesis and mitophagy were disrupted at the gene and protein levels in various human smoke exposure models, i.e. (un)differentiated primary bronchial epithelial cells exposed to cigarette smoke extract (submerged) or cigarette smoke (air–liquid interface), and peripheral lung tissue of (non-)COPD patients.

Cellular senescence, an indicator of lung ageing, is also seen as a driving mechanism involved in the pathogenesis of chronic lung diseases and considered as a potential therapeutic target [26]. Accordingly, Peter Barnes (London, UK) provided an overview of his work on senotherapies to target cellular senescence in chronic lung diseases by discussing potential therapy strategies and drugs targeting the phosphoinositide 3-kinase/mechanistic target of rapamycin (mTOR) signalling pathway (e.g. metformin and rapamycin), the senescence-associated secretory phenotype (SASP) response, activation of sirtuins (i.e. sirtuin 1 and 6), microRNAs, oxidative stress (e.g. antioxidants), mitochondrial function and senolytics [27].

The final presentation of the session was provided by Elena Lopez Rodriguez (Berlin, Germany) on air space distension preceding spontaneous fibrotic remodelling and impaired cholesterol metabolism in the absence of surfactant protein C.

Cellular senescence

Reinhold Medina (Belfast, UK) opened this session with an excellent overview of the role of endothelial cell senescence in the development of chronic diseases. He demonstrated that senescent cells cannot be defined by a single marker but rather, exhibit multiple hallmarks including growth arrest, senescence-associated β-galactosidase, DNA damage, mitochondrial dysfunction and SASP. Interestingly, a diabetic microenvironment triggers premature senescence in endothelial cells, which is associated with their decreased functionality driven by diminished mitochondrial respiration and altered mitochondrial ultrastructure. Hence, senolytic drugs specifically targeting senescent cells could be an attractive therapeutic approach for diabetes and other chronic diseases. However, their mechanism requires further study, because of potential toxicity and off-target effects. Furthermore, senolytics will likely need to be used in combination with regenerative medicine approaches to trigger the repair of the functional blood vessels.

In the second presentation, Joaquim Gea (Barcelona, Spain) summarised the newest research on the senescence of muscles during ageing and in COPD. Respiratory senescence is caused by an interplay of different factors, including genetic background, early-life exposures, diet, drugs, physical activity and comorbidities, which influence muscle structure and function [28, 29]. Muscle strength and mass physiologically decline with age at a rate that is dependent on physical activity and overall health [30]. In COPD, general loss of muscle mass is frequent, including limb, intercostal and diaphragm muscle mass. Both respiratory and limb muscles of COPD patients show oxidative stress, signs of damage and metabolic changes. Pulmonary hyperinflation and increased airway resistance, which are hallmarks of COPD, lead to additional strain and functional impairment of respiratory muscles. In turn, limb muscle dysfunction in COPD, which is characterized by a decrease in muscle strength and endurance, accompanied by lower metabolic efficiency and increased cellular senescence, directly impact the exercise capacity of the patients [31].

In the third talk, Christina Brandenberger (Hannover, Germany) presented her exciting results on the contribution of ageing to impaired alveolar repair upon injury. She investigated the functional changes in AECII, the main epithelial stem cell population of the alveoli, in an acute lung injury (ALI) model in young (3 months) and old (18 months) mice. Interestingly, she found increased senescence and DNA damage markers, accompanied by lower proliferation potential, exclusively in old AECII cells after induction of injury. Similarly, lower expression of surfactant genes and impaired surfactant function were specifically observed in old AECII compared to young AECII after injury. These important findings provide a molecular explanation for the worsened pathology and limited survival in the elderly patients suffering from ALI, and further emphasise the urgency of studying lung repair processes in old mice for better translation of lung mouse models to human pathologies.

Next, Renata Jurkowska (Cardiff, UK) presented a novel and versatile workflow based on tissue cryopreservation, which allows long-term storage of lung tissue for subsequent profiling using next-generation sequencing (NGS) [32]. She demonstrated that cryopreservation does not compromise cell viability and thereby enables isolation of multiple functional cell types (e.g. fibroblasts, bronchial epithelial basal cells and AECs) from healthy and diseased human lung. Importantly, using RNA sequencing (RNA-seq) and Illumina EPIC Array (methylation profiling), she found that genome-wide gene expression and DNA methylation signatures of isolated fibroblasts are maintained upon cryopreservation. Finally, high viability of cryopreserved lung tissue also enabled generation of excellent quality single-cell RNA-seq data from human epithelial cells, emphasising the suitability of the developed workflow for 'omics profiling of lung cells. Development of simple tissue preservation methods compatible with biobank infrastructure will empower prospective collections of viable human lung samples that could be used for cell-type resolved NGS-based profiling and disease modelling, boosting future basic and translational research.

The session was closed by Herbert Schiller (Munich, Germany), who presented data from three recent projects. Using state-of-the-art single-cell transcriptomic and proteomic profiling of young and old mice, he provided exciting insights into cellular networks during ageing [33]. He showed that ageing leads to increased transcriptional noise, altered frequency of epithelial cells in the airways and extracellular matrix remodelling. Another project, examining the kinetics of mouse lung regeneration, led to the discovery of an alveolar progenitor cell state specifically induced during injury [34]. These progenitor cells, characterised by the expression of keratin 8 (Krt8), arise from AECII cells or bronchial epithelial club cells, and differentiate into AECI cells during repair. Finally, Dr Schiller presented an ongoing project aiming to characterise mesenchymal populations of the mouse and human lung, and to investigate their role during lung repair in the bleomycin mouse model. Single-cell profiling of enriched mesenchymal cells identified several distinct cell types, including mesothelial cells, smooth muscle cells and distinctive fibroblast-like populations. Interestingly, the fibroblast subtypes all had distinct locations in the lung, indicative of specialised functions. The cellular origin of the injury-induced myofibroblasts in the human lung is currently unknown; therefore, these data will provide invaluable insights into the role of distinct fibroblasts subsets during alveolar injury and repair.

The ageing lung under stress

This session contained two presentations exploring different aspects of proteostasis during ageing and age-related chronic lung disease. Topics discussed included proteasome and immunoproteasome activity, the effects of reactive oxygen species (ROS) and other metabolites on protein degradation as well as protein oxidation and endoplasmic reticulum (ER) stress. Silke Meiners (Munich, Germany) started this session by linking proteostasis to immune activation in the ageing lung. Protein degradation in the proteasome is an integral part of proteostasis and essential for cell function. Proteostasis is tightly linked to immune cell function, as proteasomes in immune cells (immunoproteasomes) degrade proteins for display via the major histocompatibility complex (MHC). In the lung, the immunoproteasome is expressed particularly in alveolar macrophages and enables the lung to mount adaptive immune responses upon intracellular infections [35]. During ageing, the activity of the immunoproteasome is increased, which might account for increased autoimmunity during ageing, although this link needs to be further investigated. Furthermore, the immunoproteasome is increased in immune cells during ageing-associated IPF and in the bleomycin mouse model of pulmonary fibrosis [36]. Recently, Prof. Meiners has shown that ROS can affect proteostasis, while the proteasome complex becomes unstable in lung epithelial cells and mouse lungs after smoke exposure, indicating proteasome dysfunction underlying not only IPF but also COPD [37]. Ongoing projects in the Meiners laboratory include investigations into the role of mitochondrial dysfunction in cellular proteostasis and linking proteasome activity to cellular metabolism. While treatment with aspartate- or pyruvate-induced proteasome activity in fibroblasts, it was reduced by treatment with metformin. These findings open exciting new opportunities for understanding and manipulating proteostasis during ageing and ageing-associated chronic lung diseases such as IPF and COPD.

The second speaker of this session was Martina Korfei (Giessen, Germany), who presented on protein oxidation as a driver and potential target of pulmonary fibrosis. Proteins are folded and trafficked by the ER, which is dependent on a redox balance. Oxidative stress can cause protein oxidation, disrupt protein folding in the ER and result in increased ER stress. In this talk, Dr Korfei showed that protein levels of ER stress mediators are increased in lung homogenates and AECII in the lungs of IPF patients, and severe ER stress underlies AEC apoptosis and development of pulmonary fibrosis [38]. Furthermore, her research has identified specific transcription factor binding sites for induction of the proapoptotic ER stress-related transcription factor C/EBP homologous protein (CHOP). These transcription factors, activator protein 1 and c-Ets-1, are upregulated in AECII from IPF patients, while overexpression of CHOP in vitro resulted in AECII apoptosis, lung fibroblast proliferation and increased production of collagen I [39]. This indicates CHOP activation as a key process of the ER stress response and a potential driver of pulmonary fibrosis pathogenesis. Finally, using a mouse model overexpressing CHOP with a Tet-ON system in AECII specifically, she showed that CHOP overexpression in vivo in AECII resulted in apoptosis and development of pulmonary fibrosis after infection with a gammaherpesvirus. In summary, this session highlighted the importance of functional proteostasis in ageing and age-related chronic lung disease, and provided exciting new insights into the link between proteostasis, immune function and cell metabolism.

Therapeutics targeting metabolic alterations in disease

The last session of the LSC focussed on potential therapies to address metabolic alterations applied to lung inflammation and chronic diseases, such as acute respiratory distress syndrome (ARDS), COPD and IPF.

Anna Krasnodembskaya (Belfast, UK) reported exciting data regarding mesenchymal stromal cell (MSC)-mediated mitochondrial transfer as a potential therapeutic strategy to protect mitochondria from injury or enhance biogenesis in cells affected by the inflammatory environment. Through cell–cell contact or by the release of extracellular vesicles, MSCs demonstrated the ability to carry and transfer mitochondria [40], resulting in metabolic reprogramming of primary human macrophages towards an anti-inflammatory phenotype [41, 42]. Transfer in mitochondria also resulted in the restoration of mitochondrial function in primary human distal lung epithelial and endothelial cells, and alleviated mitochondrial dysfunction in the impairment of the alveolar–capillary barrier in ARDS.

In the area of chronic lung disease, Annemie Schols (Maastricht, the Netherlands) talked about how nutritional modulation could correct metabolic alterations in COPD. She demonstrated how metabolic and mechanical inefficiency may contribute to elevated energy expenditure during physical activity, and highlighted weight loss in COPD as a consequence of an imbalance between increased energy requirements and dietary intake. This leads to loss of muscle fibres and alteration of molecular markers for pathways of a mitochondrial breakdown in skeletal muscle of COPD patients, which are related to disease severity and loss of mitochondrial quantity [43, 44]. Challenges were presented and placed within the context of the future of utilising therapeutic targets that will address mitochondrial homeostasis in skeletal muscle of COPD, potentially leading towards new targets for maintaining or enhancing mitochondrial health.

The final presentation was provided by Rachel Chambers (London, UK), who presented mTOR signalling as a critical signal node during fibrogenesis in IPF [45, 46]. She highlighted that mTOR inhibition stimulated fibroblasts to restore their ability to support alveolar epithelial regeneration and proposed that targeting this axis may hold broad promise for the development of novel antifibrotic strategies, which can potentially lead to increased survival rates and improved quality of life for IPF patients. Alterations in metabolism have emerged as an additional hallmark of several lung conditions. While targeting metabolic pathways is a novel area with pre-clinical data suggesting efficacy, care must be taken to minimise adverse effects when targeting these pathways. Ideally, future (pre-)clinical studies will help to elucidate the role of cell metabolism in lung diseases and progression, and may lead to the discovery of novel therapies.

In conclusion, the overall message that permeated through the introductory lecture, as well as throughout all presentations and discussion sessions, was that metabolism and ageing are factors we need to take into account even more when designing experiments, and setting up studies and protocols. The fact that the incidence of various diseases mainly occurs in older patients should also be represented in experimental studies by making use of aged rodents. Moreover, nutrition plays an important part in these studies, and we need to consider this in our experimental setup. The use of starvation medium or supplements can have inhibitory or stimulating effects on cytokine release from cells in in vitro studies. Although it is important to see all these process in light of the complexity of the human body, it is important to also zoom in on certain mechanisms every now and then.

Early career delegates session: strategically and successfully funding your future

The topic of the LSC 2020 ECMC session was “Strategically and successfully funding your future”, and included four talks covering grant and seminar proposal writing, and different fellowship opportunities within the ERS and the European Union (EU), with the aim of helping young researchers to boost their careers. The session was opened by the current ECMC representative for Assembly 3, Niki Ubags (Lausanne, Switzerland). She provided an introduction into the ECMC, and their vision and mission [47]. Moreover, she provided insight into opportunities for ECMs to become more active and involved in ERS activities.

Reinoud Gosens (Groningen, the Netherlands) provided an overview on how to write a convincing research grant. He stressed the importance of reading the guideline of the grant that you are applying for carefully and make sure to adhere to this guideline. It was advised to first write the abstract for your grant, as this provides you with a backbone for your application, and forces you to have a structured line of thought throughout the grant and a clear problem definition. In addition, if you are not sure about an idea, pitch it to your colleagues and get their input. His last advice was, “even if you do not agree with the reviewer comments and may be disappointed with the outcome, not to be defensive to the reviewers”.

Dr Ubags also provided an overview of how to obtain a grant to organise an ERS research seminar. Like Dr Gosens, she mentioned that reading the guidelines and timely submission of the application is very important. Furthermore, it is necessary to have clear objectives, cover an unmet need, and clearly specify your target audience and the envisioned output from the seminar. This output should not be limited to a publication, you can also consider post-event activities such as a session at the International Congress. She further mentioned that it can be useful to ask the assembly heads and secretaries for input on your proposal, as they often have very valuable advice.

Next, Louise Donnelly (London, UK) talked about getting your first personal research grant within the ERS fellowship programme. She provided an overview of the different fellowship programmes that the ERS has on offer and specified the goals of these different programmes [48]. Moreover, she explained the application and interview process, and provided valuable do's and don'ts for your applications. One of these is that you must choose your keywords wisely, as this determines to which reviewers your application will be allocated. Furthermore, she stressed that it is important to make sure that your proposed work is feasible for the requested fellowship time. In addition, it is important to highlight how the fellowship will advance your career and your potential involvement in the ERS. Lastly, Dr Donnelly mentioned that it is important to not give up if you are not successful the first time. Read the feedback carefully, integrate this in a resubmission and re-apply.

Lastly, Nadia El Mjyad (Brussels, Belgium) from the EU/European Research Council (ERC) talked about funding possibilities within the EU/ERC programme. She mentioned that for ERC starting grants, the excellence of the researcher and the research proposal are the main criteria. The host institute is not taken into account. It is important to familiarise yourself with the process and all required documents early on. Moreover, when selecting a panel to which to submit an application, it can be helpful to have a look at what kind of projects have been funded before in that panel, to make sure that you chose the right panel for your application. She also mentioned that early career researchers are eligible for the ERC Synergy grant mechanism.

In conclusion, the 2020 LSC provided an overview of excellent science on metabolic alterations in lung disease and career development opportunities for ERS ECMs. We look forward to seeing you all during the LSC next year.

Key messages from scientific sessions at LSC 2020

  • Environmental and lifestyle changes affect the metabolism, and these modifications can drive changes in gene expression, which are thought to cause disease or lead to an imbalance in health status.

  • Mitochondrial dysfunction has been implicated in lung ageing and the pathogenesis of lung diseases, which indicates the potential therapeutic value of mitochondria-targeted therapies and senotherapies for lung ageing and disease.

  • Mitochondrial dysfunction can affect several key functions in different lung structural cells during the pathogenesis of lung diseases and mitochondrion-derived treatments have the potential to mitigate progress of these conditions.

  • Proteostasis, the process of protein degradation that, in immune cells, results in protein display via the MHC, is important in ageing and age-related chronic lung disease.

  • ROS and oxidative stress, such as that induced through smoke exposure, affect proteostasis, protein folding and trafficking in the ER, thereby contributing to IPF and COPD. Regulation of proteostasis by metabolites (pyruvate and aspartate) and the drug metformin offers a better understanding of the process and new therapeutic options.

  • While targeting metabolic pathways is a novel area, with pre-clinical data suggesting efficacy, care must be taken to minimise adverse effects when targeting these pathways. Moreover, the interplay between metabolic targets and current therapies could be an important therapeutic strategy to consider as more metabolism-targeting agents reach clinical trials in the future.

  • Ideally, future (pre-)clinical studies will help to elucidate the role of cell metabolism in lung diseases and progression, and may lead to the discovery of novel metabolic therapies, stratifying groups likely to benefit from specific intervention.

Take-home messages from the early career delegates session

  • Key steps in writing a convincing research grant are: 1) accurately read the guidelines; 2) start by writing a structured abstract; 3) pitch your research plan to colleagues; and 4) carefully consider reviewers’ comments to improve future or revised applications.

  • Resilience is key. Do not give up if you are not successful the first time around. Carefully review the comments and use them to improve your application.

  • Do not be discouraged to apply for funding from the ERC. If you have an outstanding project suggestion and the skills to carry out the proposed project, there are good chances to get far in the process.

Footnotes

  • Conflict of interest: P.P. Ogger has nothing to disclose.

  • Conflict of interest: J.D. Silva has nothing to disclose.

  • Conflict of interest: M. Aghapour has nothing to disclose.

  • Conflict of interest: I. Mahmutovic Persson has nothing to disclose.

  • Conflict of interest: C. Tulen has nothing to disclose.

  • Conflict of interest: R. Jurkowska reports grants from Boehringer Ingelheim Pharma GmbH & Co. KG and personal fees from BioMed X GmbH outside the submitted work.

  • Conflict of interest: N.D. Ubags has nothing to disclose.

  • Received April 13, 2020.
  • Accepted June 8, 2020.
  • Copyright ©ERS 2020
http://creativecommons.org/licenses/by-nc/4.0/

Breathe articles are open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.

References

  1. ↵
    1. O'Neill LA,
    2. Kishton RJ,
    3. Rathmell J
    . A guide to immunometabolism for immunologists. Nat Rev Immunol 2016; 16: 553–565. doi:10.1038/nri.2016.70
    OpenUrlCrossRefPubMed
  2. ↵
    1. Coll RC,
    2. Robertson AA,
    3. Chae JJ, et al.
    A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat Med 2015; 21: 248–255. doi:10.1038/nm.3806
    OpenUrlCrossRefPubMed
  3. ↵
    1. Walle LV,
    2. Stowe IB,
    3. Sacha P, et al.
    Correction: MCC950/CRID3 potently targets the NACHT domain of wild-type NLRP3 but not disease-associated mutants for inflammasome inhibition. PLoS Biol 2019; 17: e3000529. doi:10.1371/journal.pbio.3000529
    OpenUrl
  4. ↵
    1. Primiano MJ,
    2. Lefker BA,
    3. Bowman MR, et al.
    Efficacy and pharmacology of the NLRP3 inflammasome inhibitor CP-456,773 (CRID3) in murine models of dermal and pulmonary inflammation. J Immunol 2016; 197: 2421–2433. doi:10.4049/jimmunol.1600035
    OpenUrlAbstract/FREE Full Text
  5. ↵
    1. Yi YS
    . Regulatory roles of the caspase-11 non-canonical inflammasome in inflammatory diseases. Immune Netw 2018; 18: e41. doi:10.4110/in.2018.18.e41
    OpenUrl
  6. ↵
    1. Zaslona Z,
    2. Flis E,
    3. Wilk MM, et al.
    Caspase-11 promotes allergic airway inflammation. Nat Commun 2020; 11: 1055. doi:10.1038/s41467-020-14945-2
    OpenUrl
  7. ↵
    1. Simpson JL,
    2. Phipps S,
    3. Baines KJ, et al.
    Elevated expression of the NLRP3 inflammasome in neutrophilic asthma. Eur Respir J 2014; 43: 1067–1076. doi:10.1183/09031936.00105013
    OpenUrlAbstract/FREE Full Text
  8. ↵
    1. Justet A,
    2. Thabut G,
    3. Manali E, et al.
    Safety and efficacy of pirfenidone in patients carrying telomerase complex mutation. Eur Respir J 2018; 51: 1701875. doi:10.1183/13993003.01875-2017
    OpenUrlAbstract/FREE Full Text
  9. ↵
    1. Maher TM
    . Aerobic glycolysis and the warburg effect. An unexplored realm in the search for fibrosis therapies? Am J Respir Crit Care Med 2015; 192: 1407–1409. doi:10.1164/rccm.201508-1699ED
    OpenUrl
    1. Win T,
    2. Lambrou T,
    3. Hutton BF, et al.
    18F-Fluoro­deoxyglucose positron emission tomography pulmonary imaging in idiopathic pulmonary fibrosis is reproducible: implications for future clinical trials. Eur J Nucl Med Mol Imaging 2012; 39: 521–528. doi:10.1007/s00259-011-1986-7
    OpenUrlCrossRefPubMed
  10. ↵
    1. Win T,
    2. Thomas BA,
    3. Lambrou T, et al.
    Areas of normal pulmonary parenchyma on HRCT exhibit increased FDG PET signal in IPF patients. Eur J Nucl Med Mol Imaging 2014; 41: 337–342. doi:10.1007/s00259-013-2514-8
    OpenUrlCrossRefPubMed
  11. ↵
    1. Bondue B,
    2. Castiaux A,
    3. Van Simaeys G, et al.
    Absence of early metabolic response assessed by 18F-FDG PET/CT after initiation of antifibrotic drugs in IPF patients. Respir Res 2019; 20: 10. doi:10.1186/s12931-019-0974-5
    OpenUrl
  12. ↵
    1. Palsson-McDermott EM,
    2. Curtis AM,
    3. Goel G, et al.
    Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the Warburg effect in LPS-activated macrophages. Cell Metab 2015; 21: 65–80. doi:10.1016/j.cmet.2014.12.005
    OpenUrlCrossRefPubMed
  13. ↵
    1. Mills EL,
    2. Ryan DG,
    3. Prag HA, et al.
    Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1. Nature 2018; 556: 113–117. doi:10.1038/nature25986
    OpenUrlCrossRefPubMed
  14. ↵
    1. Yu XH,
    2. Zhang DW,
    3. Zheng XL, et al.
    Itaconate: an emerging determinant of inflammation in activated macrophages. Immunol Cell Biol 2019; 97: 134–141.
    OpenUrlPubMed
  15. ↵
    1. Michaeloudes C,
    2. Bhavsar PK,
    3. Mumby S, et al.
    Role of metabolic reprogramming in pulmonary innate immunity and its impact on lung diseases. J Innate Immun 2020; 12: 31–46. doi:10.1159/000504344
    OpenUrl
  16. ↵
    1. Sarode P,
    2. Schaefer MB,
    3. Grimminger F, et al.
    Macrophage and tumor cell cross-talk is fundamental for lung tumor progression: we need to talk. Front Oncol 2020; 10: 324. doi:10.3389/fonc.2020.00324
    OpenUrlCrossRef
  17. ↵
    1. Birch J,
    2. Barnes PJ,
    3. Passos JF
    . Mitochondria, telomeres and cell senescence: implications for lung ageing and disease. Pharmacol Ther 2018; 183: 34–49. doi:10.1016/j.pharmthera.2017.10.005
    OpenUrlCrossRef
  18. ↵
    1. Cloonan SM,
    2. Choi AM
    . Mitochondria in lung disease. J Clin Invest 2016; 126: 809–820. doi:10.1172/JCI81113
    OpenUrlCrossRef
  19. ↵
    1. Pan S,
    2. Conaway S Jr.,
    3. Deshpande DA
    . Mitochondrial regulation of airway smooth muscle functions in health and pulmonary diseases. Arch Biochem Biophys 2019; 663: 109–119. doi:10.1016/j.abb.2019.01.002
    OpenUrl
  20. ↵
    1. Chen Y-H,
    2. Yao W-Z,
    3. Geng B, et al.
    Endogenous hydrogen sulfide in patients with COPD. Chest 2005; 128: 3205–3211. doi:10.1378/chest.128.5.3205
    OpenUrlCrossRefPubMed
  21. ↵
    1. Perry MM,
    2. Tildy B,
    3. Papi A, et al.
    The anti-proliferative and anti-inflammatory response of COPD airway smooth muscle cells to hydrogen sulfide. Respir Res 2018; 19: 85. doi:10.1186/s12931-018-0788-x
    OpenUrl
  22. ↵
    1. James AL,
    2. Elliot JG,
    3. Jones RL, et al.
    Airway smooth muscle hypertrophy and hyperplasia in asthma. Am J Respir Crit Care Med 2012; 185: 1058–1064. doi:10.1164/rccm.201110-1849OC
    OpenUrlCrossRefPubMed
  23. ↵
    1. O'Beirne SL,
    2. Kikkers SA,
    3. Oromendia C, et al.
    Alveolar macrophage immunometabolism and lung function impairment in smoking and chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2020; 201: 735–739. doi:10.1164/rccm.201908-1683LE
    OpenUrl
  24. ↵
    1. Cloonan SM,
    2. Glass K,
    3. Laucho-Contreras ME, et al.
    Mitochondrial iron chelation ameliorates cigarette smoke–induced bronchitis and emphysema in mice. Nat Med 2016; 22: 163. doi:10.1038/nm.4021
    OpenUrlCrossRefPubMed
  25. ↵
    1. Barnes PJ,
    2. Baker J,
    3. Donnelly LE
    . Cellular senescence as a mechanism and target in chronic lung diseases. Am J Respir Crit Care Med 2019; 200: 556–564. doi:10.1164/rccm.201810-1975TR
    OpenUrl
  26. ↵
    1. Baker JR,
    2. Donnelly LE,
    3. Barnes PJ
    . Senotherapy: a new horizon for COPD therapy. Chest 2020; 158: 562–570. doi:10.1016/j.chest.2020.01.027
    OpenUrl
  27. ↵
    1. Curtis E,
    2. Litwic A,
    3. Cooper C, et al.
    Determinants of muscle and bone aging. J Cell Physiol 2015; 230: 2618–2625. doi:10.1002/jcp.25001
    OpenUrl
  28. ↵
    1. Greising SM,
    2. Ottenheijm CAC,
    3. O'Halloran KD, et al.
    Diaphragm plasticity in aging and disease: therapies for muscle weakness go from strength to strength. J Appl Physiol 2018; 125: 243–253. doi:10.1152/japplphysiol.01059.2017
    OpenUrl
  29. ↵
    1. Marcell TJ
    . Sarcopenia: causes, consequences, and preventions. J Gerontol A Biol Sci Med Sci 2003; 58: M911–M916. doi:10.1093/gerona/58.10.M911
    OpenUrlCrossRefPubMed
  30. ↵
    1. Gea J,
    2. Pascual S,
    3. Casadevall C, et al.
    Muscle dysfunction in chronic obstructive pulmonary disease: update on causes and biological findings. J Thorac Dis 2015; 7: E418–E438.
    OpenUrlPubMed
  31. ↵
    1. Prada ML,
    2. Espinet E,
    3. Mijosek V, et al.
    Versatile workflow for cell type resolved transcriptional and epigenetic profiles from cryopreserved human lung. bioRχiv 2020; pre-print [https://doi.org/10.1101/2020.04.01.018861].
  32. ↵
    1. Angelidis I,
    2. Simon LM,
    3. Fernandez IE, et al.
    An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics. Nat Commun 2019; 10: 963. doi:10.1038/s41467-019-08831-9
    OpenUrlCrossRef
  33. ↵
    1. Strunz M,
    2. Simon LM,
    3. Ansari M, et al.
    Longitudinal single cell transcriptomics reveals Krt8+ alveolar epithelial progenitors in lung regeneration. bioRχiv 2019, [https://doi.org/10.1101/705244].
  34. ↵
    1. Keller IE,
    2. Vosyka O,
    3. Takenaka S, et al.
    Regulation of immunoproteasome function in the lung. Sci Rep 2015; 5: 10230. doi:10.1038/srep10230
    OpenUrlCrossRefPubMed
  35. ↵
    1. Semren N,
    2. Welk V,
    3. Korfei M, et al.
    Regulation of 26S proteasome activity in pulmonary fibrosis. Am J Respir Crit Care Med 2015; 192: 1089–1101. doi:10.1164/rccm.201412-2270OC
    OpenUrlCrossRefPubMed
  36. ↵
    1. Kammerl IE,
    2. Caniard A,
    3. Merl-Pham J, et al.
    Dissecting the molecular effects of cigarette smoke on proteasome function. J Proteomics 2019; 193: 1–9. doi:10.1016/j.jprot.2018.12.015
    OpenUrl
  37. ↵
    1. Korfei M,
    2. Ruppert C,
    3. Mahavadi P, et al.
    Epithelial endoplasmic reticulum stress and apoptosis in sporadic idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2008; 178: 838–846. doi:10.1164/rccm.200802-313OC
    OpenUrlCrossRefPubMed
  38. ↵
    1. Klymenko O,
    2. Huehn M,
    3. Wilhelm J, et al.
    Regulation and role of the ER stress transcription factor CHOP in alveolar epithelial type-II cells. J Mol Med 2019; 97: 973–990. doi:10.1007/s00109-019-01787-9
    OpenUrl
  39. ↵
    1. Murray LMA,
    2. Krasnodembskaya AD
    . Intercellular communication via organelle transfer in the biology and therapeutic applications of stem cells. Stem Cells 2019; 37: 14–25. doi:10.1002/stem.2922
    OpenUrlCrossRef
  40. ↵
    1. Jackson MV,
    2. Morrison TJ,
    3. Doherty DF, et al.
    Mitochondrial transfer via tunneling nanotubes is an important mechanism by which mesenchymal stem cells enhance macrophage phagocytosis in the in vitro and in vivo models of ARDS. Stem Cells 2016; 34: 2210–2223. doi:10.1002/stem.2372
    OpenUrlCrossRefPubMed
  41. ↵
    1. Morrison TJ,
    2. Jackson MV,
    3. Cunningham EK, et al.
    Mesenchymal stromal cells modulate macrophages in clinically relevant lung injury models by extracellular vesicle mitochondrial transfer. Am J Respir Crit Care Med 2017; 196: 1275–1286. doi:10.1164/rccm.201701-0170OC
    OpenUrlCrossRefPubMed
  42. ↵
    1. Leermakers PA,
    2. Schols A,
    3. Kneppers AEM, et al.
    Molecular signalling towards mitochondrial breakdown is enhanced in skeletal muscle of patients with chronic obstructive pulmonary disease (COPD). Sci Rep 2018; 8: 15007. doi:10.1038/s41598-018-33471-2
    OpenUrl
  43. ↵
    1. Rabinovich RA,
    2. Bastos R,
    3. Ardite E, et al.
    Mitochondrial dysfunction in COPD patients with low body mass index. Eur Respir J 2007; 29: 643–650. doi:10.1183/09031936.00086306
    OpenUrlAbstract/FREE Full Text
  44. ↵
    1. Mercer PF,
    2. Woodcock HV,
    3. Eley JD, et al.
    Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF. Thorax 2016; 71: 701–711. doi:10.1136/thoraxjnl-2015-207429
    OpenUrlAbstract/FREE Full Text
  45. ↵
    1. Woodcock HV,
    2. Eley JD,
    3. Guillotin D, et al.
    The mTORC1/4E-BP1 axis represents a critical signaling node during fibrogenesis. Nat Commun 2019; 10: 6. doi:10.1038/s41467-018-07858-8
    OpenUrl
  46. ↵
    1. De Brandt J
    . Insight into the structure and tasks of the Early Career Members Committee of the European Respiratory Society. Breathe 2020; 16: 200046. doi:10.1183/20734735.0046-2020
    OpenUrlAbstract/FREE Full Text
  47. ↵
    1. Morty RE,
    2. Donnelly LE,
    3. Stolz D, et al.
    The ERS fellowship portfolio: fostering excellence and diversity. Eur Respir J 2019; 54: 1901503. doi:10.1183/13993003.01503-2019
    OpenUrlAbstract/FREE Full Text
PreviousNext
Back to top
Vol 16 Issue 3 Table of Contents
Breathe: 16 (3)
  • Table of Contents
  • Index by author
Email

Thank you for your interest in spreading the word on European Respiratory Society .

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Early Career Members at the ERS Lung Science Conference 2020: metabolic alterations in lung ageing and disease
(Your Name) has sent you a message from European Respiratory Society
(Your Name) thought you would like to see the European Respiratory Society web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
Citation Tools
Early Career Members at the ERS Lung Science Conference 2020: metabolic alterations in lung ageing and disease
Patricia P. Ogger, Johnatas Dutra Silva, Mahyar Aghapour, Irma Mahmutovic Persson, Christy Tulen, Renata Jurkowska, Niki D. Ubags
Breathe Sep 2020, 16 (3) 200063; DOI: 10.1183/20734735.0063-2020

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Early Career Members at the ERS Lung Science Conference 2020: metabolic alterations in lung ageing and disease
Patricia P. Ogger, Johnatas Dutra Silva, Mahyar Aghapour, Irma Mahmutovic Persson, Christy Tulen, Renata Jurkowska, Niki D. Ubags
Breathe Sep 2020, 16 (3) 200063; DOI: 10.1183/20734735.0063-2020
Reddit logo Technorati logo Twitter logo Connotea logo Facebook logo Mendeley logo
Full Text (PDF)

Jump To

  • Article
    • Abstract
    • Opening lecture
    • Immunometabolism and inflammageing
    • Mitochondrial dysfunction in lung ageing and disease
    • Cellular senescence
    • The ageing lung under stress
    • Therapeutics targeting metabolic alterations in disease
    • Key messages from scientific sessions at LSC 2020
    • Take-home messages from the early career delegates session
    • Footnotes
    • References
  • Info & Metrics
  • PDF

Subjects

  • Lung biology and experimental studies
  • Tweet Widget
  • Facebook Like
  • Google Plus One

More in this TOC Section

Expert opinion

  • Lung cancer screening by volume CT
  • In pursuit of the primary
  • A rare complication in a case of nonsmall cell lung carcinoma
Show more Expert opinion

Early career forum

  • Interview with the ECM Awardee 2022 and introducing the new ECM members
  • Preview of the 2023 LSC and Sleep and Breathing conferences
  • Overview of the ERS Clinical Practice Guidelines Methodology network
Show more Early career forum

Related Articles

Navigate

  • Home
  • Current issue
  • Archive

About Breathe

  • Journal information
  • Editorial board
  • Press
  • Permissions and reprints
  • Advertising

The European Respiratory Society

  • Society home
  • myERS
  • Privacy policy
  • Accessibility

ERS publications

  • European Respiratory Journal
  • ERJ Open Research
  • European Respiratory Review
  • Breathe
  • ERS books online
  • ERS Bookshop

Help

  • Feedback

For authors

  • Intructions for authors
  • Publication ethics and malpractice
  • Submit a manuscript

For readers

  • Alerts
  • Subjects
  • RSS

Subscriptions

  • Accessing the ERS publications

Contact us

European Respiratory Society
442 Glossop Road
Sheffield S10 2PX
United Kingdom
Tel: +44 114 2672860
Email: journals@ersnet.org

ISSN

Print ISSN: 1810-6838
Online ISSN: 2073-4735

Copyright © 2023 by the European Respiratory Society