The human eye proteome project

The human eye proteome is the latest addition to the HUPO Human Proteome Project (HPP). Semba et al. (The Human Eye Proteome Project: Perspectives on an emerging proteome. Proteomics 2013, 13, 2500–2511) establish a provisional baseline for the proteomes of the many anatomical compartments of the eye, based on literature review. As part of the Biology and Disease‐driven HPP, they and their colleagues will generate fresh data and meet the stringent guidelines for protein identification and characterization as established by the HPP.     

Saliva proteome research: current status and future outlook

Human saliva harbours proteins of clinical relevance and about 30% of blood proteins are also present in saliva. This highlights that saliva can be used for clinical applications just as urine or blood. However, the translation of salivary biomarker discoveries into clinical settings is hampered by the dynamics and complexity of the salivary proteome. This review focuses on the current status of technological developments and achievements relating to approaches for unravelling the human salivary proteome. We discuss the dynamics of the salivary proteome, as well as the importance of sample preparation and processing techniques and their influence on downstream protein applications; post-translational modifications of salivary proteome and protein: protein interactions. In addition, we describe possible enrichment strategies for discerning post-translational modifications of salivary proteins, the potential utility of selected-reaction-monitoring techniques for biomarker discovery and validation, limitations to proteomics and the biomarker challenge and future perspectives. In summary, we provide recommendations for practical saliva sampling, processing and storage conditions to increase the quality of future studies in an emerging field of saliva clinical proteomics. We propose that the advent of technologies allowing sensitive and high throughput proteome-wide analyses, coupled to well-controlled study design, will allow saliva to enter clinical practice as an alternative to blood-based methods due to its simplistic nature of sampling, non-invasiveness, easy of collection and multiple collections by untrained professionals and cost-effective advantages.     

Vaccine adjuvants: current state and future trends

The problem with pure recombinant or synthetic antigens used in modern day vaccines is that they are generally far less immunogenic than older style live or killed whole organism vaccines. This has created a major need for improved and more powerful adjuvants for use in these vaccines. With few exceptions, alum remains the sole adjuvant approved for human use in the majority of countries worldwide. Although alum is able to induce a good antibody (Th2) response, it has little capacity to stimulate cellular (Th1) immune responses which are so important for protection against many pathogens. In addition, alum has the potential to cause severe local and systemic side-effects including sterile abscesses, eosinophilia and myofascitis, although fortunately most of the more serious side-effects are relatively rare. There is also community concern regarding the possible role of aluminium in neurodegenerative diseases such as Alzheimer's disease. Consequently, there is a major unmet need for safer and more effective adjuvants suitable for human use. In particular, there is demand for safe and non-toxic adjuvants able to stimulate cellular (Th1) immunity. Other needs in light of new vaccine technologies are adjuvants suitable for use with mucosally-delivered vaccines, DNA vaccines, cancer and autoimmunity vaccines. Each of these areas are highly specialized with their own unique needs in respect of suitable adjuvant technology. This paper reviews the state of the art in the adjuvant field, explores future directions of adjuvant development and finally examines some of the impediments and barriers to development and registration of new human adjuvants.     

Mechanistic simulations of inflammation: current state and future prospects

Inflammation is a normal, robust physiological process. It can also be viewed as a complex system that senses and attempts to resolve homeostatic perturbations initiated from within the body (for example, in autoimmune disease) or from the outside (for example, in infections). Virtually all acute and chronic diseases are either driven or modulated by inflammation. The complex interplay between beneficial and harmful arms of the inflammatory response may underlie the lack of fully effective therapies for many diseases. Mathematical modeling is emerging as a frontline tool for understanding the complexity of the inflammatory response. A series of articles in this issue highlights various modeling approaches to inflammation in the larger context of health and disease, from intracellular signaling to whole-animal physiology. Here we discuss the state of this emerging field. We note several common features of inflammation models, as well as challenges and prospects for future studies.     

Microbial lipolytic fusion enzymes: current state and future perspectives

Genetic fusion of coding ORFs or connection of proteins in a post translational process are rather novel techniques to build products called fusion proteins that possess combined characteristics of their parental biomolecules. This attractive strategy used to create new enzymes not only diversifies their functionality by improving thermostability, thermo- and catalytic activity, substrate specificity, regio- or enantio-selectivity but also facilitates their purification and increases their yield. Many examples of microbial synthetic fusion biocatalysts are associated with fused enzymes that are involved in biomass degradation. However, one of the leading production segments is occupied by microbial lipolytic enzymes (lipases and esterases). As powerful biocatalysts these enzymes found their application in detergent, food, oil and fat, pulp and paper, leather, textile, cosmetics, biodiesel production industries. Moreover, lipolytic enzymes market is predicted to maintain leadership up to the year of 2024 and exceed millions of dollars. Recently, creation of lipolytic fusion biocatalysts for industrial applications gained more attention since it is not only a way of achievement of enzymes with improved properties but also a way to reduce industrial energy costs and ensure other economic benefits. This paper provides a comprehensive review on current state of microbial lipolytic fusion enzymes and their future potential.     

Standard guidelines for the chromosome-centric human proteome project

The objective of the international Chromosome-Centric Human Proteome Project (C-HPP) is to map and annotate all proteins encoded by the genes on each human chromosome. The C-HPP consortium was established to organize a collaborative network among the research teams responsible for protein mapping of individual chromosomes and to identify compelling biological and genetic mechanisms influencing colocated genes and their protein products. The C-HPP aims to foster the development of proteome analysis and integration of the findings from related molecular -omics technology platforms through collaborations among universities, industries, and private research groups. The C-HPP consortium leadership has elicited broad input for standard guidelines to manage these international efforts more efficiently by mobilizing existing resources and collaborative networks. The C-HPP guidelines set out the collaborative consensus of the C-HPP teams, introduce topics associated with experimental approaches, data production, quality control, treatment, and transparency of data, governance of the consortium, and collaborative benefits. A companion approach for the Biology and Disease-Driven HPP (B/D-HPP) component of the Human Proteome Project is currently being organized, building upon the Human Proteome Organization's organ-based and biofluid-based initiatives (www.hupo.org/research). The common application of these guidelines in the participating laboratories is expected to facilitate the goal of a comprehensive analysis of the human proteome.     

Breast cancer in sub-Saharan Africa: The current state and uncertain future

Breast cancer is the commonest cause of global cancer-related deaths in women and a public health burden in sub-Saharan Africa (SSA). Although the disease incidence in SSA seems lower, mortality rates are disproportionately high in comparison to high-income countries. The global disease burden is growing, with SSA reporting the majority of cases; however, the dearth of information results in insufficient data which is barely representative of the actual disease burden in this population. Future incidence predictions assign the subregion with a majority of the cases and associated deaths. Breast cancer presents with racial and ethnic variations, and available evidence suggests geographical diversity and persistent risk factors that have barely been explored in SSA. Breast cancer is a complex genetic disease, but the genetic risk factors in the extant African population, which is the most genetically diverse population, is scant and of low quality. This review focuses on the burden, prevalence, detection, treatment, survival, biology, as well as risk factors, and reinforces the need for breast cancer-associated risk factor investigation and population-specific studies in SSA.     

A human proteome project with a beginning and an end

Research activities centered on the ensemble of and individual human proteins have taken on numerous guises, some of which fall under the banner of what could be defined as a Human Proteome Project (HPP). However, the latter has yet to take-on the apparent global focus of its predecessor, the Human Genome Project. The reasons for this are both financial and technical. The disparate properties afforded to each protein by a 20-letter code render a single unifying approach difficult to implement, while the current limit of analytical detection has yet to deliver an entire proteome for even the simplest of microbes. The situation is complicated further by the fact that low abundance proteins dominate within any living cell. Thus, enhancement of signal-to-noise ratio by affinity ligands becomes of paramount importance if whole-organism proteomics is to be realized. The generation of such ligands (molecules exhibiting desirable affinity and selectivity for target) could provide the necessary focus and a task list with a definable beginning and end. Such a finite task list is considered essential if an HPP might one day deliver global coverage on a scale seen currently for the total DNA sequence of some 200 living organisms.     

Proteins interacting with monoamine transporters: current state and future challenges

Plasma membrane and vesicular transporters for the biogenic amines, dopamine, norepinephrine, and serotonin, represent a group of proteins that play a crucial role in the regulation of neurotransmission. Clinically, mono amine transporters are the primary targets for the actions of many therapeutic agents used to treat mood disorders, as well as the site of action for highly addictive psychostimulants such as cocaine, amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine. Over the past decade, the use of approaches such as yeast two-hybrid and proteomics has identified a multitude of transporter interacting proteins, suggesting that the function and regulation of these transporters are more complex than previously anticipated. With the increasing number of interacting proteins, the rules dictating transporter synthesis, assembly, targeting, trafficking, and function are beginning to be deciphered. Although many of these protein interactions have yet to be fully characterized, current knowledge is beginning to shed light on novel transporter mechanisms involved in monoamine homeostasis, the molecular actions of psychostimulants, and potential disease mechanisms. While future studies resolving the spatial and temporal resolution of these, and yet unknown, interactions will be needed, the realization that monoamine transporters do not work alone opens the path to a plethora of possible pharmacological interventions.     

Plants in the forest canopy: some reflections on current research and future direction

Plants are one of the sessile components of the forest canopy, and consequently quantitative studies of plant components are more widely available than for some of their mobile counterparts. From a global perspective, several exciting and innovative canopy access tools have been designed over the past few decades that have facilitated the expansion our understanding of canopy plants. These include a network of canopy cranes, the development of the French luge (or sled), and the construction of walkways and platforms for access into different levels of the canopy on a permanent basis. At the recent international forest canopy conference in Sarasota, Florida (Forest Canopies 1998: Global Perspectives, November 4–8, 1998), many canopy plant studies were presented that illustrated the achievements in this field. As co-chair at this event, I present here some reflections based on my observations of the development of canopy research between the first and second international conferences. A selection of case studies from the conference presentations are cited in this review, including: tree crown respiration studies from the crane in Panama; epiphyte ecology from walkways in Peru; insect-plant relationships in tree crowns of the USA using platforms; experimental studies of epiphytes in cloud forests using single rope techniques; and epiphyte diversity surveys in Africa. Ideas for the future are also mentioned such as the novel concept of canopy farming of orchids in Costa Rica, the linking of canopy processes to forest floor activities, and the construction of canopy walkways to provide a sustainable forest economy instead of the conventional practice of logging. The integration of research with sustainable use of forests provides a conservation theme for future canopy studies. Such new approaches to studies of canopy plants are important, as scientists increasingly play a role in global conservation policies.     

Chemotherapy of human African trypanosomiasis: current and future prospects

Three of the four currently approved drugs for the treatment of African trypanosomiasis (sleeping sickness) were developed over 50 years ago. All of the current therapies are unsatisfactory for various reasons, including unacceptable toxicity, poor efficacy, undesirable route of administration, and drug resistance. The possible modes of action of these drugs are briefly reviewed, as are the possible mechanisms of resistance. The intermediate and long-term prospects for the development of safer, effective drugs are discussed.