I am PhD student at the University of Bath working at the interface of chemistry and biology.
Molecular sensors as a diagnostic tool for non-communicable diseases
Non-communicable diseases (NCDs) are the leading cause of death in the world: 63 % of all annual deaths originate from NCD. NCD are by definition non-infectious and non-transmissible. These include heart diseases, stroke, cancer, chronic respiratory diseases and diabetes. All of these are chronic diseases, and hence, long lasting and slow in progression. NCD are of great concern in developed and underdeveloped countries. In the large majority of countries, NCD account for more than 70% of all deaths. Despite intensive research and development in the area of NCD, significant challenges in the development of new drugs, diagnostic tools and technologies remain. Given the variety of different conditions within each disease area, the geographical role also plays a significant role. Most treatments and diagnostic tools are either poorly used in developing countries since access is limited or inadequate for the NCD in this area due to considerable genetic variation and environmental factors.
The need for early detection tools has led to significant advancements in the field of molecular sensors. Molecular sensors can be designed in such a way that they are selective and sensitive to a particular target. Our group is mostly interested in exploring fluorescent molecular sensors. These rely on the on-off effect of fluorescence. Once a particular analyte comes into contact with the molecular sensor, the sensor will be switched on and emit a fluorescence signal. The main challenge with molecular sensors is to achieve selectivity and sensitivity towards a particular analyte i.e. target.
Our group is mainly interested in sensing reactive oxygen species (ROS). Increased levels of ROS have been linked to NCD in particular cancer and diabetes but also to neurodegeneration and metabolic disorders. Hence, selective and sensitive targeting of a particular ROS is highly challenging as they are very short lived species. The ultimate aim is to develop new diagnostic tools which will allow for earlier detection of NCD and consequently, allow for earlier treatment of patients and a reduced financial costs for families and the healthcare sector.
Abstract: Mitochondria cooperate with their host cells by contributing to bioenergetics, metabolism, biosynthesis, and cell death or survival functions. Reactive oxygen species (ROS) generated by mitochondria participate in stress signalling in normal cells but also contribute to the initiation of nuclear or mitochondrial DNA mutations that promote neoplastic transformation. In cancer cells, mitochondrial ROS amplify the tumorigenic phenotype and accelerate the accumulation of additional mutations that lead to metastatic behaviour. As mitochondria carry out important functions in normal cells, disabling their function is not a feasible therapy for cancer. However, ROS signalling contributes to proliferation and survival in many cancers, so the targeted disruption of mitochondria-to-cell redox communication represents a promising avenue for future therapy.
Pub.: 25 Oct '14, Pinned: 30 Aug '17
Abstract: During the last few years, the preparation of novel fluorescent probes for the selective detection of chemical species inside mitochondria has attracted considerable attention because of their wide applications in chemistry, biology, and medical science. This feature article focuses on the recent advances in the design principles and recognition mechanisms of these kinds of fluorescent probes. In addition, their applications for the detection of reactive oxygen species (ROS), nitric oxide, reactive sulfur species (RSS), thioredoxin (Trx), metal ions, anions, etc. in the mitochondrion is discussed as well.
Pub.: 24 Nov '15, Pinned: 30 Aug '17
Abstract: Reactive oxygen species (ROS) are a family of molecules that are continuously generated, transformed and consumed in all living organisms as a consequence of aerobic life. The traditional view of these reactive oxygen metabolites is one of oxidative stress and damage that leads to decline of tissue and organ systems in aging and disease. However, emerging data show that ROS produced in certain situations can also contribute to physiology and increased fitness. This Perspective provides a focused discussion on what factors lead ROS molecules to become signal and/or stress agents, highlighting how increasing knowledge of the underlying chemistry of ROS can lead to advances in understanding their disparate contributions to biology. An important facet of this emerging area at the chemistry-biology interface is the development of new tools to study these small molecules and their reactivity in complex biological systems.
Pub.: 20 Jul '11, Pinned: 30 Aug '17
Abstract: There is a vast literature on the generation and effects of reactive oxygen species in biological systems, both in relation to damage they cause and their involvement in cell regulatory and signaling pathways. The biological chemistry of different oxidants is becoming well understood, but it is often unclear how this translates into cellular mechanisms where redox changes have been demonstrated. This review addresses this gap. It examines how target selectivity and antioxidant effectiveness vary for different oxidants. Kinetic considerations of reactivity are used to assess likely targets in cells and how reactions might be influenced by restricted diffusion and compartmentalization. It also highlights areas where greater understanding is required on the fate of oxidants generated by cellular NADPH oxidases and on the identification of oxidant sensors in cell signaling.
Pub.: 19 Apr '08, Pinned: 30 Aug '17