FAQ - Answered by PharmaSea's project leader Marcel Jaspars:
We have analysed the entire marine biodiscovery pipeline and analysed the bottlenecks and will provide state-of-the-art solutions for each of these. This will hopefully make the inclusion of marine derived natural products a more attractive proposition for pharma. We will use scientific and technical fixes to optimise the process from discovery of novel microorganisms and mining their genomes to improving the chemical informatics to speed up the discovery and structural characterisation of the new compounds. Using a unique and broad array of biological assays is also important as we wish to maximise our chances of success.
- Why did you select such exotic environments to search for new compounds?
Our guiding philosophy is simple – unique/extreme environments will yield new species of marine microorganisms. For instance, rapamycin (SirolimusTM) was found from a microorganism isolated from soil collected in Easter island. By choosing deep and cold marine environments we hope to tap novel diversity not seen before. Deep ocean trenches are islands of diversity in which evolution may have progressed differently. The work on microorganisms from deep trenches shows they are indeed different. The chemistry derived from these, though limited in scope, shows high novelty.
- What kind of special equipment and methods will you use for sampling, isolation and characterisation of new microorganisms, genes, proteins, metabolites?
Access to really deep water is restricted by access to oceanography ships and deep sea sampling equipment. Our fix for this is to develop inexpensive and robust equipment based on that developed for the salvage industry. See www.deeptek.co.uk for the pictures/movies of equipment. We will use selective isolation protocols paying special attention to the nutrient environment where the sediments were collected. The use of genome scanning is vital to assess biosynthetic potential of the organisms and select only those which produce novel chemistry. The next key is in the chemical informatics and datamining – teaming up with the world’s largest free chemical database ChemSpider and the world’s top chemical software company. ACD/Labs will really help with this. Innovative zebrafish assays carried out at KULeuven will also help with the mechanism based screening of extracts and new compounds.
- How will you search for new antibiotics?
To find new species with capacity to produce new chemistry we will use selective isolation techniques, use polyphasic taxonomy and assess biosynthetic potential using genome scanning. To speed up the discovery of chemical novelty we will use chemometrics, datamining and computer aided structure elucidation. Finally, we have innovative assays and counterscreens to uncover new compounds with novel mechanisms of action.
- Why did you choose antibiotics?
There is a critical need for these recognised in the Infectious Disease Society of America’s influential report ‘Bad Bugs, No Drugs’, which led to the proposal of the 10 x 20 initiative – 10 new antibiotics by 2020. This was translated in the ESF report on Marine Biotechnology into 5 new antibiotics of marine origin by 2020, and PharmaSea is committed to help achieve that. There is no problem with SMEs involvement in the discovery of new antibiotics – they are committed to this. The current market model for antibiotics is broken and this can be fixed by new economics (much higher prices for antibiotics) or by public/private partnerships involving as in our case a blend of universities, research institutes, not for profit organisations and SMEs. We have an end user group that will help to make sure our efforts are optimised.
- What are your goals? / What do you hope to deliver?
The goals are to deliver 1 or 2 drug candidates with some preclinical evaluation carried out on them, so that the whole package may be attractive to Pharma. In addition we hope to have a number of unique compounds with associated potent and selective bioactivity which we can take forward via other mechanisms. We have decided on a very steep discovery funnel so that at each step on the most promising compounds are taken forward. To achieve this we will use a number of tools and decision procedures.
- What are the special expertises within the consortium?
We have broad expertise in almost every area of the pipeline from engineering to policy aspects of biodiscovery. We have SME/NFPs in antibiotic discovery, academic and SME expertise in molecular genetics and heterologous expression, capacity to produce at scale and expertise in natural products isolation and structural identification and as I mentioned before world beating datamining and chemical software capabilities.
- What is different to other projects that aim to find new active compounds/antibiotics in the sea and are there any overlaps or collaborations with other marine biotech consortia?
We have several members who are part of several consortia, most notably Macumba and will access their expertise via this internal mechanism. We will work with Bluegenics and SeaBioTech on legal/policy aspects as well as dissemination. Our aims in discovery differ as I understand with SeaBioTech focusing mainly on invertebrates for small molecules and enzymes and BlueGenics focusing on biomaterials. We are committed to long term maintenance of samples via OPENSCREEN and data via ChemSpider.