The exploitation of metagenomics and meta-omics approaches in life science research; community network in metagenomics

Microrganisms play a vital role in our environment they occupy a wide range of habitats from our onw gut and body surfaces all the way to hot vents under the sea, they are critical in the soil for recycling of nutrients and plant health and responsible for the essential digestion of cellulose from grass being broken down in the specialised stomach of the cow termed the rumen to the global cycling of carbon in the oceans via harvesting of sunlight as many bacteria can photosynthesize and thus harvest light energy to fix carbon dioxide. A major problem exists in our ability to study the physiology and overall activities of these microbes due to the fact that we cannot isolate and cultivate (yet) the vast majority (probably over 98%) of them in the laboratory. We know they exist because we have used methods similar to DNA forensic approaches to detect them solely based on their DNA using signature genes which allow us to identify and group them. Most of this diversity is bacterial but there are also several groups of fungi. New methods are being developed for the study of these microbial populations and this is called metagenomics so that we study the microbial community as a population of many genomes rather than trying to isolate and study one. We can study this population in our guts or in the soil by extracting and analysing DNA for diversity analysis, RNA for gene expression and protein for confirmation of activities and metabolites to determine physiology. In addition we can extract DNA and express it in other bacteria which are culturable. This allows us to capture the DNA and express it thus gaining an insight into some functions such as specific enzymes or pigments with special properties. The imof the proposed work is to establish a network of academic partners to build capacity in this important area of science to ensure that we are able to study and exploit all the interesting and exciting attributes of bacterial populations and harness them for a sustainable future.

The microbial populations existing in nature can be viewed as a community and their genomes considered as polygenomes which is the approach of metagenomics. The aim of the proposed community network is to improve our ability to use metagenomic techniques to undertake a range of research activities and within the network we aim to consider three main approaches embodied in the work packages A, B and C as follows: WPA Metagenome exploitation- expression tools; WPB Metagenomic population structure and function- pipeline tools; WPC Integration of data sets; meta-omic analysis. As a network we aim to improve existing capacity and build new and in additional develop new research tools to enable statistical and modelling analysis. The three areas will also be the subject of three main workshops held one per year over three years. Other activities will be a web site and online research tools hosted by Warwick University together with a virtual learning environment which will allow members of the network to improve their skills in analysing the complex data produced by studying metagenomic populations. The workshops will consider both statistical approaches for the in depth analysis of metagenomic DNA, RNA and protein/metabolites but also focus on the technical difficulties of the experimental work. For the full exploitation of biodiversity we need to gain access to the properties of microbial populations hence the focus on metagenomic library construction and screening for novel properties. International experts will be invited to the workshops and scientists will also be encourage to network with them and each other to build capacity. Technology transfer will also be achieved by short exchanges of personnel between universities in the network.

This research will benefit the scientific community by providing tools and guidance to how we can study uncultured biodiversity in microbial communities, and how it is possible for us to exploit these biologically diverse bacterial communities in a wide range of environments. The outputs of the network will facilitate study of microbial communities as a whole and the web site will provide guidance on how to deal with the significant diversity when working with metagenomic DNA, RNA and proteins and or metabolites.
Meta-omics is in its infancy and has only very recently been applied to the study of microbial communities but promises to be a valuable complement to the latest extraction and analysis of metagenomic DNA. Guidance, online tools and capacity building for the development and application of these cutting-edge techniques will provide important information for other life scientists trying to disentangle the relationship between members of microbial communities and also their interactions with their hosts or other members of the environment such as plant roots, insects and other eukaryotes.
Guidance on new approaches to exploiting metagenomic libraries and Identification of novel genes and enzymes will be of interest to biotechnology companies. The general public have an interest in their gut microbiota, but also in microbial interactions with plants and animals. Synthetic biology approaches will seek to exploit and manipulate these communities to reduce our dependence on chemicals, drugs and make a more sustainable future.
Outreach activities from the project will provide answers to the way in which we can study the uncultured majority of bacteria and exploit their diversity.