Systems biology approach to Wilson’s disease

Wilson’s disease (WD) is a severe disorder of copper misbalance, which manifests with a wide spectrum of liver pathology and/or neurologic and psychiatric symptoms. WD is caused by mutations in a gene encoding a copper-transporting ATPase ATP7B and is accompanied by accumulation of copper in tissues, especially in the liver. Copper-chelation therapy is available for treatment of WD symptoms and is often successful, however, significant challenges remain with respect to timely diagnostics and treatment of the disease. The lack of genotype-phenotype correlation remains unexplained, the causes of fulminant liver failure are not known, and the treatment of neurologic symptoms is only partially successful, underscoring the need for better understanding of WD mechanisms and factors that influence disease manifestations. Recent gene and protein profiling studies in animal models of WD began to uncover cellular processes that are primarily affected by copper accumulation in the liver. The results of such studies, summarized in this review, revealed new molecular players and pathways (cell cycle and cholesterol metabolism, mRNA splicing and nuclear receptor signaling) linked to copper misbalance. A systems biology approach promises to generate a comprehensive view of WD onset and progression, thus helping with a more fine-tune treatment and monitoring of the disorder.     

Systems biology of the secretory pathway: What have we learned so far?

Several RNAi screens were performed in search for regulators of the secretory pathway. These screens were performed in different organisms and cell lines and relied on different readouts. Therefore, they have only little overlap among their hits, leading to the question of what we have learned from this approach so far and how these screens contributed towards an integrative understanding of the endomembrane system. The aim of this review is to revisit these screens and discuss their strengths and weaknesses as well as potential reasons for their failure to overlap with each other. As with secretory trafficking, RNAi screens were also performed on other cellular processes such as cell migration and autophagy, both of which were shown to be intimately linked to secretion. Another aim of this review is to compare the outcome of the RNAi screens on secretion, autophagy and cell migration and ask whether the functional genomic approaches have uncovered potential mechanistic insights into the links between these processes.     

Is biology science?

Yes of course it is, you reply, and so do I. But, are we in a minority in recognizing that the life sciences can be hard science?     

Technological biology? Things and kinds in synthetic biology

Social scientific and humanistic research on synthetic biology has focused quite narrowly on questions of epistemology and ELSI. I suggest that to understand this discipline in its full scope, researchers must turn to the objects of the field—synthetic biological artifacts—and study them as the objects in the making of a science yet to be made. I consider one fundamentally important question: how should we understand the material products of synthetic biology? Practitioners in the field, employing a consistent technological optic in the study and construction of biological systems, routinely employ the mantra ‘biology is technology’. I explore this categorization. By employing an established definition of technological artifects drawn from the philosophy of technology, I explore the appropriateness of attributing to synthetic biological artifacts the four criteria of materiality, intentional design, functionality, and normativity. I then explore a variety of accounts of natural kinds. I demonstrate that synthetic biological artifacts fit each kind imperfectly, and display a concomitant ontological ‘messiness’. I argue that this classificatory ambivalence is a product of the field’s own nascence, and posit that further work on kinds might help synthetic biology evaluate its existing commitments and practices.     

Are we doing synthetic biology?

Synthetic Biology is a singular, revolutionary scenario with a vast range of practical applications but, is SB research really based on engineering principles? Is it contributing to the artificial synthesis of life or using approaches “sophisticated” enough to fall outside the scope of biotechnology or metabolic engineering? We have reviewed the state of the art on synthetic biology and we conclude that most research projects actually describe an extension of metabolic engineering. We draw this conclusion because the complexity of living organisms, their tight dependence on evolution and our limited knowledge of the interactions between the molecules they are made of, actually make life difficult to engineer. We therefore propose the term synthetic biology should be used more sparingly.     

Cancer immunotherapy: simply cell biology?

There is a clear need for improved cancer therapy and survival rates. Effective immunotherapy would be the treatment modality of choice from several viewpoints, and dendritic cell (DC)-based immunotherapy is emerging as the most promising approach to cancer immunotherapy. However, the plethora of approaches to DC-based cancer therapy now threatens to impede the development of an effective immunotherapy regime, as competing egos and commercial interests masquerade as scientific rigour. Here, I argue that the current controversies regarding the numerous approaches reflect the paucity of our immunological understanding, and present a simple cell biological analysis that defines the rationale for the development of effective cancer immunotherapy.     

How can ontologies help vector biology?

The reach of genomics has now extended to vector biology, with three mosquito genomes already sequenced and more arthropod vector genomes in the pipeline. The availability of these genomes has paved the way for high-throughput investigations on genome-wide gene expression and proteomics in vector biology. Such investigations would not have been possible without parallel progress in bioinformatics. It is now necessary to construct specific ontologies that will enable vector biologists to achieve computer-comprehensible annotation of genes and genomes, but also of various experimental, clinical and surveillance data. This will inevitably lead to the enhanced usage of such controlled vocabularies, and to an effort to develop novel ontologies, particularly in the context of disease control.     

Is there a special conservation biology?

Conservation biology is special to the extent that it fills useful roles in the scientific and conservation fields that are not being filled by practitioners of other disciplines. The emergence of the “new conservation biology” in the late 1970's and its blossoming in the 1980's and 1990's reflect, to a large degree, a failure of traditional academic ecology and the natural resource disciplines to address modern conservation problems adequately. Yet, to be successful conservation biology, as an interdisciplinary field, must build on the strengths of other disciplines both basic and applied. The new conservation biology grew out of concern over extinction of species, although the field has expanded to include issues about management of several levels of biological organization. I examine four controversial questions of importance to conservation biologists today: 1) are there any robust principles of conservation biology? 2) Is advocacy an appropriate activity of conservation biologists? 3) Are we educating conservation biologists properly? 4) Is conservation biology distinct from other biological and resource management disciplines? I answer three of these questions with a tentative “yes” and one (3) with a regretful “in most cases, no.” I see a need for broader Training for students of conservation biology, more emphasis on collecting basic field data, compelling applications of conservation biology to real problems, increased influence on policy, and expansion of the international scope of the discipline. If all these occur, conservation biology will by truly special.     

Interdisciplinary integration in biology? An overview

Philosophical theories about reduction and integration in science are at variance with what is happenign in science. A realistic approach to science show that possibilities for reduction and integration are limited. The classical ideal of a unified science has since long been rejected in philosophy. But the current emphasis on interdisciplinary integration in philosophy and in science shows that it survives in a different guise. It is necessary to redress the balance, specifically in biology. Methodological analysis shows that many of the grand interdisciplinary theories involving biology actually represent pseudo-integration covered up by inappropriate, overgeneral concepts. Integrationism is not bad, but it must be kept within reasonable bounds. If the present analysis is appropriate, there will have to be fundamental changes in research strategy both in science and in the philosophy of science.