Best Poster Awards – Metabolism Meets Epigenetics

In its first edition, the EMBO|EMBL Symposium: Metabolism Meets Epigenetics brought together 289 world-leading researchers who examined how metabolites and metabolic networks impact gene regulation, what their roles are in disease and how this opens novel therapeutic avenues.

In addition to the 21 invited speakers and 22 selected short talks, 142 posters were presented during the two poster sessions. Today we present three of the five award-winning posters decided by popular vote.

Citrate carrier links intermediate metabolism to histone acetylation upon ageing of mouse mesenchymal stem cells (MSCs)

PHOTO: Andromachi Pouikli

Authors: Andromachi Pouikli (1), Monika Maleszewska (2), Swati Parekh (1), Chrysa Nikopoulou (1), Maarouf Baghdadi (1), Linda Partridge (1), Peter Tessarz (1)

Chromatin and metabolism interact in a reciprocal manner; on one hand metabolism-related genes are subjected to epigenetic modifications, which regulate gene expression. On the other hand, intracellular metabolism provides metabolites which can serve as essential co-factors and substrates for chromatin-modifying enzymes, affecting their activity. Although, it is well established that the process of ageing is accompanied by changes in metabolism and by chromatin alterations, their interplay in this context remains still poorly understood. In this study we sought to determine how ageing impinges on the relationship between cellular metabolism and the epigenome, using mouse mesenchymal stem cells from the bone marrow (BM-MSCs). In brief, our data suggest that there is a strong and direct link between the metabolic and the epigenetic states of the cell, with ageing-driven changes in metabolism regulating gene transcription and BM-MSC’s stemness, via alterations of the chromatin structure. We conclude that physiological ageing elicits changes in metabolism, resulting in suppressed glycolysis and impaired lipid biogenesis. Moreover, we demonstrate that during ageing there are lower levels of histone acetylation, despite the higher acetyl-CoA levels. We provide a solid explanation for this apparent discrepancy, pointing to the impaired export of acetyl-CoA from mitochondria to the cytosol. Indeed, the protein levels of the citrate carrier Slc25a1 decrease dramatically upon ageing. Using inhibition and supplementation experiments we provide a causal relationship between Slc25a1 function and the levels of histone acetylation, which directly influence chromatin accessibility and plasticity. Collectively, our data establish a tight, age-dependent connection between metabolism, epigenome and stemness and identify citrate carrier as the responsible protein for the mitochondrial-nuclear communication.

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(1) Max Planck Institute for Biology of Ageing, Germany, (2) Personalis Inc, Germany


Epigenetics meets metabolism through histone acetyltransferase NAA40

PHOTO: Christina Demetriadou

Authors: Christina Demetriadou (1), Anastasia Raoukka (1), Agathi Elpidoforou  (1), Constantine Mylonas (2), Swati Parekh (2), Peter Tessarz (2), Antonis Kirmizis (1)

N-alpha-acetyltransferase 40 (NAA40) is distinct among other histone acetyltransferases (HATs) because it deposits an acetyl moiety on the alpha-amino group at the very N-terminal tip of histones H4 and H2A, instead on the lysine side chain. The biological function of this evolutionarily conserved enzyme remained unexplored for several decades because it was thought to mediate an inert modification. However, we previously showed that NAA40-mediated N-terminal acetylation of histone H4 (N-acH4) crosstalks with an adjacent arginine methylation mark to regulate yeast cellular aging in response to caloric restriction through transcriptional control of several metabolic genes. Therefore, we are currently interested in deciphering the function of human NAA40 in carcinogenesis. We recently showed that NAA40 is frequently upregulated in primary human colorectal cancer (CRC) samples. Remarkably, depletion of NAA40 and its accompanied reduction in N-acH4 blocked colon cancer cell proliferation and reduced cell survival in vitro and in xenograft models. We also found that loss of NAA40 expression or of its HAT activity markedly induce global histone methylation. Additionally, whole transcriptome analysis showed that NAA40 knockdown leads to upregulation of key enzymes involved in one-carbon metabolism. Intriguingly, silencing of methylenetetrahydrofolate reductase (MTHFR), which links the folate to methionine cycle, rescues the induction of global histone methylation and loss of cell viability triggered by NAA40 depletion. Hence, this recent work implies that NAA40 may transcriptionally regulate vital metabolic enzymes to control the flux of carbon units into the methionine cycle influencing S-adenosylmethionine (SAM) levels and triggering epigenome reprogramming of cancer cells. Overall, our findings thus far propose that NAA40 and its associated N-acH4 are crucial epigenetic modulators in tumourigenesis and implicate these factors in rewiring cancer cell metabolism.

Poster currently not available.

(1) University of Cyprus, Cyprus
(2) Max Planck Institute for Biology of Ageing, Germany


Role of MOF acetyl transferase in mitochondrial homeostasis

PHOTO: Sukanya Guhathakurta

Authors: Sukanya Guhathakurta (1), Christoph Martensson (2), Alexander Schendzielorz (3), Bettina Warsheid (3), Thomas Becker (2), Asifa Akhtar (1)

Mitochondria lies at the centre of cellular and organismal energy homeostasis, housing a large repertoire of enzymes that are required for the synergy of various metabolic pathways. Mitochondrial gene expression and protein acetylation are two important fundamental processes situated at the crossroad between mitochondrial function and metabolic status of a cell. Gene transcription in the mitochondria has been studied over several decades, but enzymatic acetylation of mitochondria proteins has stayed so far enigmatic. MOF acetyl transferase and its KANSL complex members dually localize to the nucleus and the mitochondria in mouse and human cells. The MOF-KANSL complex regulates metabolic gene transcription in the nucleus and expression of Electron Transport Chain (mtETC) components from the mtDNA, in a cell type dependent fashion. Regulation of nuclear gene transcription by MOF is well understood, however, its control of mitochondrial function remains elusive. Here, we report that loss of MOF leads to severe mitochondrial dysfunction in Mouse Embryonic Fibroblasts (MEFs), sprouting from a stalled oxidative phosphorylation. We address the mechanisms by which the enzyme maintains mitochondrial function in these cells by using a multi-omics approach. We discovered that the role of MOF-KANSL complex in the mitochondria of aerobically respiring cells could be decoupled from its regulation of steady state RNA levels, and could further be attributed to the acetylation of mitochondrial proteins. We characterize the role of acetylation on these proteins through generation of acetylated and non-acetylated mimics. Collectively our data, along with previously published works, suggests that MOF has emerged as a moderator to strike a harmony in the context of communication between the nucleus and the mitochondria. Recent progress on the project will be discussed.

(1) Max Planck Institute for Immunobiology and Epigenetics, Germany
(2) Institute of Biochemistry and Molecular Biology, Germany
(3) Institute for Biology II, Germany

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Best Poster Awards – Precision Health

140 researchers came together recently at the EMBL Advanced Training Centre in Heidelberg, Germany, for the EMBO Workshop: Precision Health: Molecular Basis, Technology and Digital Health (13 – 16 November 2019) to present and discuss the promises and challenges of precision health and the molecular insights necessary to enable a maintenance of wellness and prevention of disease.

Out of the posters presented, 4 were awarded a poster prize based on popular vote. Here we present the poster abstracts of four of the winners.

A computational modelling approach to characterizing postprandial glucose responses in individuals
Balazs Erdos from TiFN Wageningen and MaCSBio, Maastricht University, The Netherlands, PHOTO: Balazs Erdos

Balazs Erdos (1), (2)*, Bart van Sloun (1), (2), Shauna O’Donovan (2), Michiel Adriaens (2), Natal van Riel (3), Ellen Blaak (4), Ilja Arts (2)

The large variability in the dynamic properties of the postprandial glucose response curves in individuals suggest that it is not sufficient to use average values or single time point measures of postprandial glycemia in order to characterize individuals’ glycemic control. Instead, approaches that are capable of capturing the dynamic events are necessary. In this study, we develop personalized computational models based on ordinary differential equations, to describe the glucose and insulin dynamics of individuals in response to an oral glucose tolerance test. We observed that these personalized models are capable of capturing a wide range of glucose and insulin dynamics including normal, prediabetic and type 2 diabetic responses as well as responses from intermediate states.

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(1) TiFN, Wageningen, The Netherlands, (2) Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, The Netherlands, (3) Dept. of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands, (4) Dept. of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands

*E-mail: balazs.erdos@maastrichtuniversity.nl


Predict nephrotoxicity associated with cisplatin-based chemotherapy in testicular cancer patients

Sara Garcia (1), Jakob Lauritsen (2), Zeyu Zhang (3), Mikkel Bandak (2), Marlene Danner Dalgaard (1), Rikke Linnemann Nielsen (1), Gedske Daugaard (2), Ramneek Gupta (1)

In industrialized countries, testicular cancer (TC) is the most common solid tumor in men between 20 and 40 years old and besides being one of the most treatable types of cancer, the long-term side-effects of chemotherapy are worrisome, since they are largely irreversible. Their severity is normally related to the total amount of chemotherapy received, which makes that an important factor to a successful treatment. The standard treatment for TC is 3 cycles of cisplatin, etoposide and bleomycin (BEP), being that the number of cycles can vary between 4-5 or more if the prognosis of the patient is intermediate or poor. Some of the late side-effects include nephrotoxicity, which can be measured by the drop in glomerular filtration rate after the patient follows chemotherapy. Materials and Methods: Integrative machine learning models were built using a dataset of 400 Danish individuals in order to identify clinical and/or genomics features and classify patients at higher risk of developing nephrotoxicity given a treatment of BEP-cycles. Results: First, only clinical features, such as age at the time of treatment, dose of cisplatin, patient’s prognosis, and number of cycles, were considered, and relevant features were selected to use in the classifier (AUC 0.66, SD 0.02). The classifier was then optimized by adding genomics markers, which helped improving the prediction (AUC 0.75, SD 0.02). Conclusions: Therefore, it is proposed a machine learning algorithm which, by helping predicting nephrotoxicity in advance, can benefit to improve chemotherapy efficacy in TC patients. These data driven models can also be applicable to other cancers, such as ovarian, bladder, and lung cancer where more elderly patients are at risk of nephrotoxicity and identification upfront will have direct clinical implications.

Poster currently not available

(1) Technical University of Denmark, Denmark, (2) Copenhagen University Hospital, Denmark, (3) University of Chinese Academy of Sciences, China


Loss of N-glycanase 1 alters transcriptional and translational regulation
Petra Jakob from EMBL Heidelberg, Germany, PHOTO: Petra Jakob

Petra Jakob (1), William Mueller (1), Sandra Clauder-Münster (1), Han Sun (2), Sonja Ghidelli-Disse (3), Diana Ordonez (1), Markus Boesche (3), Markus Bantscheff (3), Paul Collier (1), Bettina Haase (1), Vladimir Benes (1), Malte Paulsen (1), Peter Sehr (1), Joe Lewis (1), Gerard Drewes (3), Lars Steinmetz (1)

N-Glycanase 1 (NGLY1) deficiency is an ultra-rare, complex and devastating neuromuscular disease. Patients display multi-organ symptoms including developmental delays, movement disorders, seizures, constipation and lack of tear production. NGLY1 is a deglycosylating protein involved in the degradation of misfolded proteins retrotranslocated from the endoplasmic reticulum (ER). NGLY1-deficient cells have been reported to exhibit decreased deglycosylation activity and an increased sensitivity to proteasome inhibitors. We show that the loss of NGLY1 causes substantial changes in the RNA and protein landscape of K562 cells and results in downregulation of proteasomal subunits, consistent with its processing of the transcription factor NFE2L1. We employed the CMap database to predict compounds that can modulate NGLY1 activity. Utilizing our robust K562 screening system, we demonstrate that the compound NVP-BEZ235 (Dactosilib) promotes degradation of NGLY1-dependent substrates, concurrent with increased autophagic flux, suggesting that stimulating autophagy may assist in clearing aberrant substrates during NGLY1 deficiency.

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(1) EMBL Heidelberg, Germany, (2) Stanford University, United States of America, (3) Cellzome, Germany


Data integration for prediction of weight loss in clinically controlled dietary trials

Rikke Linnemann Nielsen (1), Marianne Helenius (1), Sara Garcia (1), Henrik Munch Roager (2), Derya Aytan (3), Lea Benedicte Skov Hansen (1), Mads Vendelbo Lind (2), Josef Vogt (1), Marlene Danner Dalgaard (1), Martin I Bahl (3), Cecilia Bang Jensen (1), Rasa Muktupavela (1), Christina Warinner (4), Vincent Appel (5), Rikke Gøbel (5), Mette B Kristensen (2), Hanne Frøkjær (6), Morten H Sparholt (7), Anders F Christensen (7), Henrik Vestergaard (5), Torben Hansen (5), Karsten Kristiansen (6), Susanne Brix Pedersen (1), Thomas Nordahl Petersen (3), Lotte Lauritzen (2), Tine Rask Licht (3), Oluf Pedersen (5), Ramneek Gupta (1)

Diet is a key strategy in weight loss management. Advances in omics technologies research allow analyses of determinants of clinical interventions outcomes. We have previously reported diet-induced weight loss in non-diabetic middle-aged Danes in two clinically controlled dietary trials where the content of whole grain or gluten was changed. However, it remains elusive how predictable weight loss is at the individual level. We here classify weight loss responders and non-responders from the whole grain and gluten trials by integrating multi-omics data (host genetics, gut microbiome, urine metabolome) together with physiology and anthropometrics into random forest models. The most predictive models for weight loss included features of diet, gut microbial species and urine metabolites (ROC-AUC:0.84-0.88, model only with diet type ROC-AUC:0.62). Furthermore, we demonstrate that a model ensemble is robust to missing information of microbiome and metabolome profiles given features of physiology (including postprandial response), host genetics and transit-time (ROC-AUC:0.72).

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(1) Technical University of Denmark, Denmark, (2) University of Copenhagen, National Food Institute, Technical University of Denmark, Denmark, (3) National Food Institute, Technical University of Denmark, Denmark, (4) Harvard University, United States of America, (5) The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Denmark, (6) University of Copenhagen, Denmark, (7) Bispebjerg University Hospital, Denmark


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How does the environment play a role in biodiversity?

Biodiversity – in all its forms and interactions – is the variety of life on Earth. Climate change is exacerbating biodiversity loss, and vice versa. Ahead of the EMBO | EMBL Symposium ‘The Organism and its Environment’ (1–4 March 2020), we talk to Scientific Organiser and EMBL Director General Edith Heard about the impact the environment has on biodiversity and the role of research in solving global challenges.

Does the environment play a large role in the creation of biological diversity?

Biodiversity is the variety of life on Earth. This life, in all its shapes and sizes, occurs in the context of ecosystems: it relies on and interacts with other organisms and the physical environment. Biodiversity represents the collective ‘knowledge learned’ by evolving species over millions of years, about how to survive the vastly varying environmental conditions Earth has and is experiencing. These varying environmental conditions cause natural variations in biodiversity, as well as genetic and epigenetic changes, within and between species over time. Today, scientists are trying to understand the basis of these natural variations, as they will allow us to understand how life evolves.

Fish populations have declined at an alarming rate, and half the world’s shallow water coral reefs have been lost in just 30 years.

But biodiversity is also a measure of the health of any ecosystem. Recent trends in biodiversity loss show very clearly that humans are destroying ecosystems on a massive scale. According to the Director General of the World Wildlife Fund (WWF), increased pollution, deforestation, climate change and other manmade factors have created a “mind-blowing” crisis. The WWF Living Planet Report 2018 (WWF LPR, 2018) also states that freshwater fish populations have declined by more than 80% on average since 1970 and half of the world’s shallow water coral reefs have been lost in the last 30 years (WWF LPR, 2018). Alongside this, deforestation of tropical rainforests means we are currently losing more than 100 species of plants and animals a day (Holley, 2017). In short, human’s influence on the environment greatly impacts biodiversity and we are currently burning the library of life.

How can you determine the effect of the environment on an organism?

The environment can affect an organism in a multitude of ways. The impact can be transient or longer term; within an individual or across generations. The environment can also lead to molecular, cellular, physiological or behavioural changes. For example, the expression of genes in an organism can be influenced by the external environment, such as where the organism develops or factors associated with where it is located. Gene expression could also be influenced by an organism’s internal environment, including hormones or metabolism. Finally, the genome itself – genetic factors that vary between individuals in natural populations – could also influence gene expression.

Research groups at EMBL look at how variety in organisms comes about

Untangling the impact of genetic and environmental variation can be very challenging and for a long time, scientists have tended to focus on minimising variations in the environment in order to understand how changes in genotype affect phenotype. This, alongside the deeply embedded “one genotype = one phenotype” metaphor, has meant that environmentally induced phenotypic variation has been ignored in favour of ‘‘more useful and precise’’ study of genetic polymorphisms. This is despite the fact that from as far back as the early 1900s, scientists have known that the phenotype of an individual depends on the interaction between its genotype and environmental cues! Today, we finally have the power to consider the impact of the environment on phenotype. We can make precise measurements at the molecular, cellular and organism scales in controlled environments that can be varied and we can sequence genomes at the same time.

We can also take human data paired with environmental data – for example in the context of some of EMBL’s research interests such as infectious disease and microbiomes – to understand the quantitative effects of the environment and its influence on human biology. Pioneering projects such as Tara Oceans have also allowed us to research the interactions between organisms and the environment by generating reference data, discovering emergent ecological principles and developing predictions about how ecosystems will be affected by a changing environment. Understanding how organisms exist together and in changing environments is of fundamental importance for our understanding of biological principles and our knowledge of life.

What challenges are currently being faced in this field?

Studying organisms in their environment will become increasingly important.

Understanding the behaviour of individual molecules, cells or whole organisms is already challenging. Understanding how the environment influences an organism – or populations of organisms – represents a whole new scale in complexity. This is an area that I think EMBL could uniquely contribute to in the future. It will be necessary to shift from researching organisms mainly in the laboratory to studying them in their environment. We will also need to ensure the rapid development of technologies and tools to meet these scientific needs. Alongside this, we need new approaches to integrate large, complex data sets and make sense of them. To rise up to this challenge, we need theory. We are now in a unique position to address the dynamics and complexity of living matter across multiple scales and in the context of changing environment. But we need theory to address societal and planetary issues too. We must aim for a rate of scientific discovery that outpaces the rate of calamity such as biodiversity loss, ecosystem degradation, epidemics and climate change.

What can be done to prepare for the future with regard to biological diversity, the organism and its environment?

Research, research and more research! Environmental problems such as the hole in the ozone layer or acid rain were solved by sound scientific approaches. We need to learn from these past scientific and societal successes. Today the ever-increasing numbers of new technologies are allowing us to collect, measure and store data at unprecedented scales. We also need to bring ecologists, zoologists, population geneticists and environmental experts together to address these research questions. Together we can apply cutting-edge technology with rigour, attract new scientific talent and disseminate knowledge to global communities.

What inspired you to organise this symposium?

As a geneticist and epigeneticist, I have explored the intersection between genotype and the environment and how that produces a phenotype. From observing many areas of research – ranging from social insects such as bees and ants, to plant vernalisation and variations between identical twins – I felt that the time is ripe to bring together scientists from many different areas. I also wanted this to be a symposium that would attract scientists from different areas to EMBL.

At EMBL, we want to understand the molecular basis of life. Until now, EMBL has been known for exploring genomic, molecular, structural and cell biology at the level of individual organisms. Looking ahead, we want to study organisms in the context of their physical and biological environments not just in isolation. In order to truly understand life on Earth, we need to study organisms in nature, not just in the lab. One way to understand life at the molecular level will be to try to bring relevant ecosystems back to the lab, to measure and perturb them under controlled conditions. The speakers we’ve invited are experts from many different areas of biology or ecology, and will bring exciting new perspectives to our research.

The EMBO|EMBL Symposium: The Organism and its Environment will take place at EMBL Heidelberg, Germany, from 1-4 March 2020

What is the greatest benefit of this symposium for the scientific community?

The symposium is an opportunity to address how organisms are influenced by a changing environment. It will bring together different research disciplines and go beyond pure genetic or ecological perspectives of phenotypic variation. Geneticists, molecular biologists, evolutionary biologists and ecologists do not necessarily meet under ordinary circumstances. This meeting will enable such interactions and cross-fertilisation.

What will be the main highlight of the symposium?

Today we are in a unique position to address the complexity and dynamics of life at multiple scales, from molecules to ecosystems. We also need to consider the idea that change including in the environment is not necessarily a bad thing. After all, without change, evolution could not occur and none of the amazing biodiversity of life on our planet would exist! I hope that a highlight of this symposium will be some wonderful new insights into evolutionary processes.

 

References

Holley D., (2017). General Biology II, Organisms and Ecology. Indianapolis: Dog Ear Publishing, 898.

World Wildlife Fund, (2018). Living Planet Report: Aiming higher [PDF] https://wwf.panda.org/knowledge_hub/all_publications/living_planet_report_2018/ [Accessed 25 July 2019].

https://wwf.panda.org/knowledge_hub/all_publications/living_planet_report_2018/

However the WWF DG is quoted by several articles as describing the crisis as mind-blowing, for example: “https://www.voanews.com/science-health/report-earth-has-lost-60-percent-its-wildlife-1970

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BioMalPar’s most loyal friends

Meet Prof. Peter Preiser and Dr. Stefan Rahlfs, two of BioMalPar’s most loyal participants, who have not missed a conference since 2009 and 2010 respectively. They recount their experience from previous events of the series and share with us their expectations of the upcoming conference.

How has the conference developed over the years in your opinion and what makes you come back every year?

PP: The BioMalPar conference is unique in that it is one if not the only annual conference that focuses on the molecular and cellular aspects of the malaria parasite. It therefore has always represented an ideal meeting to catch up with the latest developments in the field. Due to its focus on giving PhD students a chance to present their work the meeting always had a “new” feel to it which I particularly appreciated.

SR: The conference has always drawn participants from all over the world, and presented interesting talks by both experienced and young researchers. However, getting to the conference venue used to be much more difficult and the early events took place in office rooms and a tent (it was pretty hot in there!). But things have changed significantly since then. Now there is a new parking garage, a new conference centre, which I like very much – light, modern, scientific.  The best part is the “helix” where you have to find your way walking on a base pair bridge .

PP: Clearly the conference has changed over time – this was partly due to the end of the EU funded BioMalPar programme and therefore the discontinuation of the PhD programme, but still it retained its focus on giving young researchers an opportunity to present their work. Today the meeting is a nice balance between young and more established researchers, which means there are the hot-off-the-press type presentations representing the work of a single researcher along with the more comprehensive research achieved through a multi-team effort.

SR: The quality of the talks remains impressive with a good mixture of topics. There is always a keynote lecture followed by short talks. Workshops and flash talks are now included and I have learned a lot about different people especially the ones receiving the Lifetime achievement award.

PP: The establishment of the Lifetime achievement award was something that I felt was particularly important as it provided many of the young researchers attending the meeting a perspective of the immense contributions the previous, slightly older generation had made to the field.

What’s the best memory you have of a BioMalPar conference?

PP: For me it has always been the relaxed attitude of the meeting and the opportunity to discuss science over a beer at the posters or outside (weather permitting) on a mild spring evening. Many fantastic ideas were generated through these discussions.

SR: The things that always stay in my mind are the fantastic venue, attractive program, nice age-mixture of people and the friendly atmosphere. I always go home with respect for others’ work but also with new ideas for my own research. At one of the BMP conferences I personally met Prof. Hagai Ginsburgh, and once he combined his stay in Germany with a trip to our Giessen-University for some days. This was very impressive and constructive at the same time.

In your opinion, what challenges is malaria research facing and how does coming to BioMalPar address these problems?

PP: I think the effort to control and eliminate malaria has made significant progress and we are now getting to a critical phase in the global effort. It is now important to ensure that efforts to control the disease are not slackened and that funders continue to support this important health initiative. From a research perspective we still have key challenges in terms of drug resistance and the lack of an efficient vaccine, not to mention the issue of P. vivax. It is particularly in these areas where BioMalPar can stimulate the right discussions and interactions that will eventually lead to significant benefits in controlling the disease.

SR: It is still a disease occurring in poor countries and resistance is always a problem. Although bed nets help a lot and a vaccine is available (which is not very effective, but the best mankind has been able to provide so far), research must go on. And in rural areas infrastructure for distribution of newly developed drugs or vaccines needs to be installed. For research there is a gap between industry (monetary research) and universities (basic research), which is due to their different settings.

Looking at the programme of this year’s conference, what do you think will be the highlight and what would you like to see in the next edition in 2020?

PP: This is hard to say as based on the titles there appear to be many new and exciting topics on the programme. I am quite intrigued about the work going on with the mosquito vector and possible ways a better understanding in this area may provide us with better tools for intervention. I am also excited about the use of stem cells to study malaria parasites, as this technology would significantly help me to address some of the questions I am interested in.

I think one of the key things that I would like to see develop more in the future is a better link between the basic research presented at the BioMalPar conference and how this could be utilised in a more clinically relevant context. For example, how does our understanding of malaria immunology help in developing a better vaccine or how do we use the vast amounts of genomic data more effectively for the discovery of new drugs, new vaccine targets or even better diagnostic markers. Some of this is already happening but a lot more can be done.

Prof. Preiser, you will present a short talk titled “Comparative mapping of Plasmodium proteomes provides new insights into erythrocyte remodelling”.  What can participants expect to learn from your talk?

I have always wondered about how the malaria parasites changes its host cell. In particular, I was intrigued about the apparent differences that different malaria parasite species have developed in modifying the same type of host cell. However, most of our knowledge on this is based on the study of a single parasite species P. falciparum. My lab has therefore tried to develop new approaches to study the differences the different plasmodium species have developed by using human, simian and rodent malaria parasite species and identify all the different proteins that the parasite exports into the host cell. This approach has given us some very surprising results that I will talk about during the meeting.

Dr. Rahlfs, you will present a poster titled “Glucose 6-phosphate dehydrogenase 6-phosphogluconolactonase: characterization of the Plasmodium vivax enzyme and inhibitor studies”.  Can you give us a short preview of your poster?

As a member of the “Becker-lab” in Giessen we are focusing on redox metabolism as drug target and on redox regulations in general and under stress. A number of gene knockouts of our group but also others mostly do not have big impact (due to redundancy), but the importance of the Glucose 6-phosphate dehydrogenase 6-phosphogluconolactonase (GluPho) in P. falciparum has been demonstrated by a lethal phenotype. Now we would like to expand this knowledge also on P. vivax. We cloned P. vivax glucose 6-phosphate dehydrogenase (PvG6PD), the C-terminal and NADPH-producing part of PvGluPho, recombinantly produced it in Escherichia coli, purified and characterised the enzyme. IC50 values of several compounds were determined on P. vivax G6PD, inhibitors that had been previously characterised on PfGluPho.

 

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Celebrating 15 years of BioMalPar

In honour of World Malaria Day and ahead of the 15th annual EMBL conference on the Biology and Pathology of the Malaria Parasite (BioMalPar), we spoke to the conference organisers Richárd Bártfai, Kirk Deitsch and Lyn-Marie Birkholtz, as well as Andy Waters from the BioMalPar steering committee – which is responsible for selecting the scientific organisers each year – to find out where the field is heading.

Richárd Bártfai, Lyn-Marie Birkholtz, Kirk Deitsch and Andy Waters

 

The BioMalPar conference is celebrating its 15th anniversary this year. How did it all start and how has it developed over the years?

AW: I was part of the organisation of the original meeting in 2004 and have attended every iteration since.  It was originally a dual-purpose meeting designed to bring together the participants in the EC funded Network of Excellence of the same name, “BioMalPar”, the students in the associated PhD school that it funded, and to serve as an international meeting on malaria.

LB: I started attending BioMalPar in 2006 and was inspired by the format of the conference, allowing such great interaction and exposure to young scientists. It always allows the most cutting edge (mostly unpublished) research to be presented, and the addition of workshops to the conference programme allows for additional opportunities for learning, and these workshops are new and trending every year.

2018 BioMalPar conference at the EMBL Advanced Training Centre

What inspired you to organise this conference?

LB: This meeting to me is THE malaria conference that I annually attend. As a researcher from a malaria endemic country, I was inspired to organise the conference to strengthen exposure of the great research performed in such countries at the conference, and provide context for the research findings to show how the excellent research presented have direct impact to people’s lives living with malaria.

RB: This meeting is a prime example of a community effort. Hence organising it is an honour and a great way to serve our community. I very much enjoyed the collegial and welcoming atmosphere created by former organisers and I hope that we will manage to recreate some of it this year as well.

KD: In recent years, the conference has become more widely attended by non-European scientists and is now an event attended by investigators from throughout the world. When I was invited to participate in the organisation of this year’s meeting, I considered it an exceptional opportunity to interact with international colleagues and build stronger ties for exchanging ideas and potential collaborations.

The format of the conference is a bit distinct from that of other meetings in that the majority of talks are reserved for selected short talks. What is the benefit for the programme to have mostly selected talks?

KD: Reserving the majority of each session for short talks ensures that the latest, unpublished data will be presented at the meeting. Highlighting young investigators presenting new data for the first time also lends an air of excitement to the sessions that adds to the overall “buzz” of the conference.

LB: This is in my opinion one of the main strengths of the conference. The audience will have the ability to hear new data ‘straight from the horses mouth’ as the short talks are mostly presented by early career scientists and mostly covers unpublished work.

AW: The emphasis is on packing in as much new science by the early career researchers as possible.  This format makes it possible and allows one to work to themes in terms of the meeting organisation

RB: We will have excellent keynote lectures this year to set the stage and provide broad overviews on specific subjects. Yet, selected talks offer opportunity to young research fellows to share their exciting, unpublished findings.

The poster sessions allow researchers to present their findings

The short talk selection for this year’s edition has now been finalised. Could you share what the focus and highlights of the conference will be?

RB: The content of the short talks is traditionally kept secret till the start of the meeting and I do not want to break this tradition ;-). But we as organisers had a hard time to make a selection out of the numerous excellent abstracts submitted, so I am certain that the scientific standard of the meeting will be very high.

LB: As organisers, we were very happy to have a large basis of excellent abstracts to select from, which will make the final choices exciting to come and listen to!

In your opinion, what challenges is malaria research facing and how close are we to an effective malaria vaccine?

KD: Everyone in the field is thrilled that a malaria vaccine is now being deployed for the first time. However, we also recognise that this vaccine has significant shortcomings in terms of its efficacy and longevity of protection. Research into the nature of the immune response of people infected by malaria parasites, as well as identifying new drugs and drug targets and methods of vector control will all contribute to our ability to control the disease.

LB: With the trial roll out of the RTS,S malaria vaccine in Malawi, we are indeed closer to evaluating the large scale effect of this intervention. However, malaria is a very complicated disease and we should continue with our multifaceted integrative control strategies, which will possibly be the only way we can really have an impact towards elimination. Our research challenges remain to inform policy makers as to the importance of continued funding of the work and for the research community to continue translating these to tangible outcomes, as we have done successfully for the past decade.

RB: Despite substantial progress in the last decades elimination of malaria is still out of our reach. Integration of insight gained in various fields will be essential for generating breakthroughs in drug/vaccine development and vector control alike. The BioMalPar meeting certainly provides an excellent platform for the exchange of innovative ideas and hence will help to bring the well-desired goal of malaria elimination closer to reality.

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