Food contains different types of fat. There are some suggestions that not all the fats are equal and that there is good and bad fat with respect to their effects in the body. Not too much is known about what fat normally does in the cells of the body. We know that fat can be stored, burned, been sent from one organ to another within the body and more importantly fat are important 'bricks' to build up the different components of the cells. Interestingly not all the fats have the same size, the length of some fats is longer than others and we think that the length of the fat species may be an important determinant whether fat is stored or burn. The best organ to study this is a special type of organ known as brown fat present in children and small animals. This organ can do both, making fat and burning fat so it is the ideal organ to investigate the effect of fat length on these two processes. To study fat length we will investigate the effect of lack and/or excess of Elovl6, a molecule that elongates fat from 12 carbons to 18 carbons. Specifically we propose to investigate: 1) if making fat longer can alter the development of the brown fat organ; b) whether eliminating/increasing the capacity of elongating fat makes the animals fatter/leaner and c) less/more capable of making heat. To that end we will use cells and mice in which we will decrease or increase the capacity to make fat longer and then study the type of fat these animals make using very novel techniques that allow us to know all the types of fats that these animals will have. This information will inform us about which fats are good and which ones are bad and will allow us, for example, to modify the diets of humans and animals to ensure that they have the right type of fats to remain healthy.

The long-term science for this project is directed towards the preparation of new and effective therapeutics, and to dothis we need to ensure that our novel devices hit their biological targets and have proven efficacyin a particular disease application before we can commence a larger programme to guide theirdevelopment towards clinical practice. The European Science Foundation (ESF) Nanomedicine Forward Look describes the development ofnew multifunctional, spatially ordered, architecturally-varied systems for targeted drug delivery as apriority. Nanopharmaceuticals based on antibody-drug conjugates and polymer-biopolymerconjugates are a key component of enhanced efficacy medicines. While more complex, theseconjugates offer enhanced diversity, leading to drugs with much higher information content comparedto small molecule compounds. This allows for greater target specificity, improved functionality andthe opportunity to multi-task, for example to diagnose and treat in situ, or to act on more than onetherapeutic target or disease pathway simultaneously. The novel conjugate nanodevices we willprepare in this programme are thus uniquely able to address diseases which are inadequately treatednow. By exploiting new biological targets and interfaces, our materials will contribute a vital step inimproving patient, economic and society outcomes arising from disease.