ESR1: Grant Garren January, IBP-CNR
ESR2: Kevin A. Martinez Andrade, SZN
ESR3: Yannik Schneider, UiT
ESR4: Antigoni-Angeliki Kyritsi, University of Aberdeen
ESR5: Florent Magot, GEOMAR
ESR6: Arianna Guisti, KU Leuven
ESR7: Sloane Patry, University College Cork
ESR8: Jane Collins, ABS-int & KU Leuven
ESR9: Maria Kokkini, Fundación MEDINA
ESR10: Asimenia Gavriilidou, WUR
ESR11: Alejandro Moreiras Figueruelo, Italbiotech & ICB-CNR
ESR1- Grant Garren January was born and bred in Cape Town, South Africa and currently he is conducting his PhD at the Institute of Protein Biochemistry at the National Research Council of Italy (IBP-CNR) in Naples.
PhD title: Exploitation of new strains for drug discovery from deep-sea sediments
Currently, multi-drug resistant (MDR) infections are a primary concern for the World Health Organization (WHO) and society as a whole. Microorganisms, such as human pathogenic bacteria have developed resistance to antibiotics primarily through the misuse and over use of these drugs. The WHO reports that as of 2017, approximately 700 000 deaths are attributed to antimicrobial resistance (AMR), and this number has been projected to increase exponentially up to 10 million per annum by 2050. Therefore, the search for novel compounds with activity to AMR is a priority for the EU, the WHO, and other research bodies. Current antibiotics are no longer effective against MDR organisms, and therefore new drugs with novel modes of action are required to treat these infections.
Extreme environments, such as Antarctic, harbour a diverse range of microorganisms that have over the course of evolution developed molecular adaptations to these cold environments. The unique metabolism of these microorganisms includes secondary metabolites that have been reported to possess several bioactivities, including anti-microbial and anti-biofilm activities. During this PhD study, microbial diversity and metabolic potential of Antarctic deep-sea sediments will be explored for pharmaceutical and biotechnological applications. Particularly, this research will focus on improving the culturabilty of the uncultivable fraction from environmental samples, so as to enrich for bioactive producing strains. The hypothesis is that these as-yet-to-be cultured strains possess new/novel marine natural products that could combat AMR.
Follow Grant on Twitter https://twitter.com/TheGarrenXXVII, LinkedIn https://www.linkedin.com/in/grant-garren-january-0b537734/ and Researchgate https://www.researchgate.net/profile/Grant_January.
For more information, please contact Grant using the following email address: email@example.com
ESR2- Kevin A. Martinez Andrade grew up in Colombia and Spain and he is a PhD student at the Stazione Zoologica Anton Dohrn (SZN) in Italy.
PhD Title: Drug discovery from marine microalgae
Marine microalgae are considered a potentially new and valuable source of biologically active compounds for applications in several biotechnology sectors. They can be easily cultured (compared to other microorganisms), have short generation times and enable an environmentally-friendly approach to drug discovery by overcoming problems associated with the over-utilization of marine resources and the use of destructive collection practices. Marine organisms have the capacity to produce a variety of biologically potent natural products, including antimicrobial and anticancer compounds. With much of the biodiversity in the ocean still unknown and rapid progress being made in the field of marine exploration technology, there is significant potential for the discovery of new biological resources with applications in medicine.
The general aim of this project is to select biologically active marine microalgae with anti-cancer activity for the identification of bioactive compounds to be used as potential new drugs. Selected species will be cultivated in various culturing conditions in order to increase the probability of production of interesting compounds. Cultivation will be performed in small-medium volumes, but scale-up in huge volumes (100L-photobioreactors) will be used to obtain higher quantities of the compounds of interest. Extracts and fractions will be prepared from microalgal biomass and screened against a panel of cancer and normal cells. Active extracts and fractions will be further analysed in order to identify the active compounds. An additional aim will be to unravel the mechanism of action of the active compounds and the main pathways involved in cell death processes.
Follow Kevin on LinkedIn https://www.linkedin.com/in/kevin-andrés-martínez-andrade-3b4b10113.
ESR3- Yannik Schneider comes from Germany and he is currently doing his PhD at the University of Tromso in Norway.
PhD Title: Trials to isolate and investigate novel chemical entities out of marine microorganisms with anti-bacterial and anti-proliferative effect.
There has been a considerable increase in serious antibiotic-resistances observed in clinics during the last decades in which the development of new antibiotics has been neglected. Beside infectious diseases, cancer is another threat for human’s live, especially solid tumors, where small molecular therapy still seems to be the most promising available approach. Therefore, new therapeutic molecules and lead structures are highly desirable in those fields. In the 1990’s the pharmaceutical development expended great effort into the field of combinatorial chemistry and “random screening”, retrospectively, we can conclude that despite the great efforts in combinatorial chemistry, natural sources are furthermore promising to be investigated in particular because of their success in providing new active compounds and lead structures compared to the combinatorial approach. While plants and terrestrial microorganisms have been a valuable source for drugs far beyond “traditional medicine,” taking in account drugs like Methylergomethrine (postpartum hemorrhage), Cyclosporine (immunosuppressive) or Paclitaxel (cancer), just to name a few examples. A relatively unexplored field are marine organisms; however, the available examples indicate that pharmaceutically active compounds out of marine microorganisms have a higher bioactivity and show unique structures and effects, not observed in their terrestrial counterparts. Therefore, marine microorganisms seem to be an ideal research-subject for search new active compounds and lead structures. During my work, I will search for compounds with anti-bacterial and anti-proliferative effect out of marine bacteria. The used techniques comprise chemical purification guided by bioassays and mass spectrometry and nuclear magnetic resonance for structure elucidation as well as genome mining. Beside the compounds, the biosynthetic pathways are also of interest, since the production-feasibility of a certain molecule and the knowledge about involved enzymes is desirable.
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To find out more, please contact Yannik using the following email address:firstname.lastname@example.org
ESR4- Antigoni Kyritsi comes from Nafplio, Greece and is working on her PhD at the Marine Biodiscovery Centre, University of Aberdeen, in Scotland.
PhD Title: Marine organisms have the capacity to produce a variety of biologically potent natural products, including antibiotic and anticancer compounds.
The main aim of my PhD is the identification of lead compounds from organisms obtained from extreme habitats. These organisims will be grown under a range of culture conditions to give rise to complex metabolic profiles representing a range of biosynthetic pathways.
Liquid Chromatography Mass Spectrometry (LC-MS) based dereplication will be applied to identify the extracts most likely to contain novel chemical entities. Compounds will be isolated from promising extracts and dereplicated using molecular formula and basic, 1-dimensional Nuclear Magnetic Resonance (NMR) data from the 1H and 13C NMR spectra. Elucidation of the 2-dimensional structure of lead compounds will be done using spectroscopic methods (NMR and Mass Spectroscopy). Determination of the relative stereochemistry will be conducted using the most appropriate approach for the structural class under study.
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ESR5- Florent Margot is from France and now based in Kiel, Germany conducting his PhD at GEOMAR Centre for Marine Biotechnology.
PhD Title: Enhanced chemical diversity of antibiotic molecules from extremophilic microorganisms monitored by metabolomics and chemical imaging
Oceans cover more than 70% of the earth and encompass variable habitats concerning salinity, temperature, pressure, light availability. The deep sea (>1000 m water depth) constitutes more than 60% of the ocean´s biosphere and harbors an unparalleled biodiversity. It constitutes an extreme habitat due to high pressure, darkness and often low nutrient and oxygen concentrations. In order to ensure their survival, microorganisms thriving in such environments have to develop unique metabolic adaptations, thus represent an interesting resource for the discovery of new molecules. However, due to access difficulties to deep-sea habitats and the lack of suitable and affordable sampling techniques, deep-sea microorganisms have remained untapped for their potential in marine biodiscovery.
In this study, we obtained deep-sea sediment samples from Arctic Ocean (-2432 m), sampled by an remotely operated vehicle during RV Polarstern expedition 108. The selected microorganisms will be cultured in several conditions including different: nutrient sources (OSMAC approach), use of epigenetics modifier and co-cultivation. All of this study is focus on one point: enchanced chemical diversity of antibiotic. Bioactive strains will be regrowth in large-scale, the isolation and characterization of the bioactive compounds will be achieved by chromatographic technique.
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For further information, contact Florent at the following e-mail address: email@example.com.
ESR6- Arianna Giusti is italian and is working on her PhD with the Laboratory for Molecular Biodiscovery at KU Leuven in Belgium.
PhD Title: Safety assessment of potential leads using zebrafish based assays
The estimated cost for bringing a new drug to the market exceeds US 1$ billion per drug and can take up to 17 years. Still, the average percentage of a drug succeeding through the Research and Development (R&D) process is only 10%. The drug discovery process hence constitutes an enormous investment in time and money for the pharmaceutical industry. Despite this effort, however, more than 220 approved drugs have been withdrawn from the market since 1953 due to safety concerns. Among the toxicities observed, drug-induced liver injury (DILI) is the most common reason for failures during the drug development process and for safety-related withdrawal of drugs from the pharmaceutical market. Other common reasons for drugs being withdrawn from the market are cardio-, neuro- and nephrotoxicities. Therefore, having access to robust, valid and high-throughput toxicity tests in the early stage of development to exclude drug candidates with adverse effects would be highly beneficial.
Nowadays, the classical first approach in toxicity investigation consists of enzymatic or culture-based in vitro screenings, but these often provide insufficient information since they are not complex enough to assess the absorption, distribution, metabolism and excretion (ADME) mechanisms. On the other hand, it is not possible to utilize mammalian models in early stages of drug discovery. Large or medium screens would be too time demanding, costly, and in addition interfere with the welfare of the animals. A way to combine the cost effective and high throughput approach with the complexity of an in vivo animal system in the field of drug discovery has been realized by using zebrafish larvae. Zebrafish larvae are small (they fit 96-384 well plates thus allowing high-throughput assays), similar to mammals biologically and developmentally and they produce a large number of offspring (200-300 eggs per mating) which develop rapidly ex utero (vital organs are formed within 5 days). In addition, embryos and larvae are semi-transparent which facilitates the assessment of lead compounds.
The aim of this PhD project is to assess the safety of lead compounds isolated by the other members participating in the ITN European project “MarPipe”. This will be accomplished by setting up and establishing suitable assays to assess general toxicity and cardio-, nephro-, neuro-, hepatotoxicity assays specifically.
For further information, please contact Arianna using the following email address: firstname.lastname@example.org.
ESR7- Sloane Patry comes from France and now lives in Ireland, conducting her PhD at the School of Microbiology, University College Cork.
PhD title: Genomic mining to identify novel biosynthetic pathways from bioactive compounds in marine bacterial strains.
Antibiotic resistance is a major threat to public health worldwide. The number of pathogens developing resistance to standard drugs is increasing day by day. The principal goal of this PhD is the discovery of new bioactive compounds that will lead to the formation of new antibiotics to fight against the antibiotic resistance crisis. Marine organisms are an interesting source of novel bioactive compounds because they can survive in extreme conditions (temperature, pressure, thermal vents). Also, microbes that live in marine sponges are exposed to a very competitive environments which encourages the production of antibiotic compounds. One of the most famous producers of antibiotics are Streptomyces species. By focusing on Streptomyces samples taken from sponges in marine environments we hope to identify novel bioactive compounds who will hopefully lead to the formation of new antibiotics.
The main objectives of this PhD are:
– The identification of molecular target of already identified lead compounds with antibacterial activity.
– Characterization of new bacterial strains.
– Description of a variety of metabolic pathways involved in the production bioactive agents.
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To find out more, please contact Sloane using the following email address: email@example.com.
ESR8- Jane Collins is from the UK and is now based in Belgium, conducting her PhD with ABS-int and KU Leuven.
PhD title: Unlocking Marine Genetic Resources – Streamlining the Legal, Policy and Business Aspects of the Marine Biodiscovery Pipeline
Marine organisms have the capacity to produce a variety of biologically potent natural products, including antimicrobial and anticancer compounds. With much of the biodiversity in the ocean still unknown and rapid progress being made in the field of marine exploration technology, there is significant potential for the discovery of new biological resources with applications in medicine. Rates of marine resource exploitation are therefore likely to increase in the future, expanding into previously inaccessible parts of the ocean. Challenges associated with utilisation of marine genetic resources are not only related to physical access, but are also strongly linked to law, policy and business.
1) to study the legal and policy frameworks governing marine biodiscovery (from sample to product). Attention will be given to potential options for access and benefit-sharing linked to the utilisation of marine genetic resources in areas beyond national jurisdiction
2) to investigate intellectual property protection, business models and innovation management for different stages of the marine biodiscovery value chain. This will involve a review of successful and failed marine biotechnology case studies
By addressing a combination of cross-cutting legal, policy and business issues, this project aims to provide new insight into factors that may create an enabling environment for marine biodiscovery.
Follow Jane on LinkedIn http://bit.ly/2AXntZ1 and Twitter @JaneEvaCollins.
ESR9- Maria Kokkini comes from Athens, Greece and now is working on her PhD at the Fundación MEDINA in Granada, Spain.
PhD title: Scale-up of production, modification and determination of the preclinical safety of antimicrobial hits isolated from marine microorganisms
Antimicrobial resistance (AMR) is one of the biggest threats to global health nowadays. It may occur naturally over time, usually through genetic changes, but the human factor is accelerating this process and clearly driving the evolution of resistance. The antibiotic resistance crisis reflects the worldwide overuse and misuse of these drugs, as well as the lack of development of new antibiotic agents by the pharmaceutical industry. For this reason, the discovery and development of new sources of antibiotics has become an essential matter concerning human health. Although microorganisms in terrestrial environments continue to be the main source of new metabolites, the search is being expanded to include marine microorganisms. Their ability to survive in extreme habitats enables marine microorganisms to develop unique physiological and metabolic capabilities, leading to the production of metabolites which may not be found in terrestrial environments.
A family of new compounds belonging to the spirotetronate structural class has been identified from extracts of a marine actinomycete. These compounds are potentially new antimicrobial leads against antibiotic-resistant pathogens. Consequently, there is an interest in improving their production and determining their preclinical safety. Scaled-up fermentations in selected conditions to be determined will yield multi-milligram amounts of the desired hits, which will then be used as a starting point for the generation of new and improved derivatives using biotransformation and/ or semi-synthetic approaches. The biological profile of the compounds will be evaluated against an extended panel of microbial pathogens and completed with determination of the preclinical safety and toxicity tests that will permit the selection of the best candidates to be developed as potential leads.
Follow Maria Kokkini on Researchgate: https://www.researchgate.net/profile/Maria_Kokkini2.
To find out more, please contact Maria using the following email address: firstname.lastname@example.org.
ESR10- Asimenia Gavriilidou grew up in Thessaloniki, Greece and now lives in the Netherlands conducting her Phd at the Laboratory of Microbiology in Wageningen University & Research.
PhD Title: Cultivation and characterisation of novel marine microorganisms with high potential as sources of bioactive compounds
Discovery and development of new types of compounds of biomedical importance have become top priority in the combat against certain global health issues. Marine sponges are considered as the most prolific reservoir of natural products, yielding pharmaceutically interesting compounds. Marine bio-discovery has shifted its focus towards sponge-associated microbes as they are suspected to be the actual producers of these important metabolites. However, the limited success in the in vitro cultivation of sponge-associated microbes remains a major bottleneck in this field. A promising strategy to unravel their biotechnological potential is the application of novel cultivation techniques coupled with the valuable information offered by the ‘omics’ methods. Nevertheless, actual examples of attempts to link meta-omics with microbial cultivation are scarce.
To address this gap, first objective of this PhD project is to explore the genome of metabolically interesting sponge-derived isolates already available in the MIB strain collection. The next step is to investigate the holobiont of a cold-water sponge of the N. Atlantic deep-sea (Geodia barretti), a known source of a wide range of secondary metabolites with important pharmaceutical properties. We will combine novel high-throughput cultivation strategies (e.g. microcultivation and microprinting on culture chips) with knowledge derived from state-of-the-art ‘omics’ methods. Ultimate goal of this study is the generation of a strain collection of novel marine microorganisms with high potential of producing pharmaceutically promising bioactive compounds.
ESR11- Alejandro Moreiras Figueruelo comes from Spain and is currently working on his PhD at Consorzio Italbiotec and CNR-Institute of Biomolecular Chemistry (ICB-CNR) in Italy.
PhD title: Drug-discovery from marine natural compounds.
Drugs are an essential tool of modern medicine for tackling some diseases, and the search for new molecules with better properties seems to be a never-ending challenge. One of the classic sources of new drugs is nature. This approach to the discovery of new molecules consists of testing a high number of extracts from diverse organisms against a particular disease and hoping to find in some of them a positive activity. Those displaying positive activity will be selected for further work, however that phase of research is out of the scope of this particular project.
Together with the detection of activity, another essential step in drug discovery is the isolation of the active compound from all the other existent molecules. The compound of interest may be very scarce, and during the isolation process a great portion could be lost. For those reasons, a preliminary fractionation method was developed in such a way that the molecules of each extract would be separated into five groups according to their solubility. This way, the processing is simplified, the recovery rate of the molecules is higher and the processed samples are more convenient for further manipulation.
Approximately 60 marine organisms will be obtained, extracted, pre-fractionated and tested in this project. In addition, these extracts will form the starting point of an extract library which will be established in the institution for further research.
Connect with Alejandro on LinkedIn https://www.linkedin.com/in/alejandromoreiras/.
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