Studies of Complex Biological Systems with Applications to Molecular Medicine: The Need to Integrate Transcriptomic and Proteomic Approaches

2014 ◽  
pp. 57-98
2014 ◽  
pp. 29-70
Author(s):  
Elena Silvestri ◽  
Assunta Lombardi ◽  
Pieter De Lange ◽  
Daniela Glinni ◽  
Rosalba Senese ◽  
...  

2011 ◽  
Vol 2011 ◽  
pp. 1-19 ◽  
Author(s):  
Elena Silvestri ◽  
Assunta Lombardi ◽  
Pieter de Lange ◽  
Daniela Glinni ◽  
Rosalba Senese ◽  
...  

Omics approaches to the study of complex biological systems with potential applications to molecular medicine are attracting great interest in clinical as well as in basic biological research. Genomics, transcriptomics and proteomics are characterized by the lack of ana prioridefinition of scope, and this gives sufficient leeway for investigators (a) to discern all at once a globally altered pattern of gene/protein expression and (b) to examine the complex interactions that regulate entire biological processes. Two popular platforms in “omics” are DNA microarrays, which measure messenger RNA transcript levels, and proteomic analyses, which identify and quantify proteins. Because of their intrinsic strengths and weaknesses, no single approach can fully unravel the complexities of fundamental biological events. However, an appropriate combination of different tools could lead to integrative analyses that would furnish new insights not accessible through one-dimensional datasets. In this review, we will outline some of the challenges associated with integrative analyses relating to the changes in metabolic pathways that occur in complex pathophysiological conditions (viz. ageing and altered thyroid state) in relevant metabolically active tissues. In addition, we discuss several new applications of proteomic analysis to the investigation of mitochondrial activity.


Author(s):  
Henry S. Slayter

Electron microscopic methods have been applied increasingly during the past fifteen years, to problems in structural molecular biology. Used in conjunction with physical chemical methods and/or Fourier methods of analysis, they constitute powerful tools for determining sizes, shapes and modes of aggregation of biopolymers with molecular weights greater than 50, 000. However, the application of the e.m. to the determination of very fine structure approaching the limit of instrumental resolving power in biological systems has not been productive, due to various difficulties such as the destructive effects of dehydration, damage to the specimen by the electron beam, and lack of adequate and specific contrast. One of the most satisfactory methods for contrasting individual macromolecules involves the deposition of heavy metal vapor upon the specimen. We have investigated this process, and present here what we believe to be the more important considerations for optimizing it. Results of the application of these methods to several biological systems including muscle proteins, fibrinogen, ribosomes and chromatin will be discussed.


Author(s):  
Nicholas J Severs

In his pioneering demonstration of the potential of freeze-etching in biological systems, Russell Steere assessed the future promise and limitations of the technique with remarkable foresight. Item 2 in his list of inherent difficulties as they then stood stated “The chemical nature of the objects seen in the replica cannot be determined”. This defined a major goal for practitioners of freeze-fracture which, for more than a decade, seemed unattainable. It was not until the introduction of the label-fracture-etch technique in the early 1970s that the mould was broken, and not until the following decade that the full scope of modern freeze-fracture cytochemistry took shape. The culmination of these developments in the 1990s now equips the researcher with a set of effective techniques for routine application in cell and membrane biology.Freeze-fracture cytochemical techniques are all designed to provide information on the chemical nature of structural components revealed by freeze-fracture, but differ in how this is achieved, in precisely what type of information is obtained, and in which types of specimen can be studied.


1990 ◽  
Vol 78 (1) ◽  
pp. 1-1
Author(s):  
M. J. Brown

From this issue, Clinical Science will increase its page numbers from an average of 112 to 128 per monthly issue. This welcome change — equivalent to at least two manuscripts — has been ‘forced’ on us by the increasing pressure on space; this has led to an undesirable increase in the delay between acceptance and publication, and to a fall in the proportion of submitted manuscripts we have been able to accept. The change in page numbers will instead permit us now to return to our exceptionally short interval between acceptance and publication of 3–4 months; and at the same time we shall be able not only to accept (as now) those papers requiring little or no revision, but also to offer hope to some of those papers which have raised our interest but come to grief in review because of a major but remediable problem. Our view, doubtless unoriginal, has been that the review process, which is unusually thorough for Clinical Science, involving a specialist editor and two external referees, is most constructive when it helps the evolution of a good paper from an interesting piece of research. Traditionally, the papers in Clinical Science have represented some areas of research more than others. However, this has reflected entirely the pattern of papers submitted to us, rather than any selective interest of the Editorial Board, which numbers up to 35 scientists covering most areas of medical research. Arguably, after the explosion during the last decade of specialist journals, the general journal can look forward to a renaissance in the 1990s, as scientists in apparently different specialities discover that they are interested in the same substances, asking similar questions and developing techniques of mutual benefit to answer these questions. This situation arises from the trend, even among clinical scientists, to recognize the power of research based at the cellular and molecular level to achieve real progress, and at this level the concept of organ-based specialism breaks down. It is perhaps ironic that this journal, for a short while at the end of the 1970s, adopted — and then discarded — the name of Clinical Science and Molecular Medicine, since this title perfectly represents the direction in which clinical science, and therefore Clinical Science, is now progressing.


2019 ◽  
Vol 3 (5) ◽  
pp. 435-443 ◽  
Author(s):  
Addy Pross

Despite the considerable advances in molecular biology over the past several decades, the nature of the physical–chemical process by which inanimate matter become transformed into simplest life remains elusive. In this review, we describe recent advances in a relatively new area of chemistry, systems chemistry, which attempts to uncover the physical–chemical principles underlying that remarkable transformation. A significant development has been the discovery that within the space of chemical potentiality there exists a largely unexplored kinetic domain which could be termed dynamic kinetic chemistry. Our analysis suggests that all biological systems and associated sub-systems belong to this distinct domain, thereby facilitating the placement of biological systems within a coherent physical/chemical framework. That discovery offers new insights into the origin of life process, as well as opening the door toward the preparation of active materials able to self-heal, adapt to environmental changes, even communicate, mimicking what transpires routinely in the biological world. The road to simplest proto-life appears to be opening up.


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