Grand challenges in cellular biochemistry: the "next-gen" biochemistry.

Abstract

It is said that Biochemistry is a young scientific discipline, making its “formal” debut toward the end of the 1900th century (Manchester, 2000), with seminal works by Buchner (1897, Jaenicke, 2007), (Pasteur and Berthelot, 1906), Hill (1898), Embden and Glaessner (1901), Meyerhof (1911), Parnas (1911), Harden (1911), and, of course, Michaelis and Menten (Johnson, 2013; Michaelis and Menten, 2013; Deichmann et al., 2014). These early and important contributions marked the road for future work in the fields of (a) chemical and biochemical structures and associated functions by Sanger (1945), Perutz (1942), Franklin (1950), Watson and Crick (1953), Pauling et al. (1949, 1951), Pauling and Corey (1951), Zuckerkandl and Pauling (1962), Kornberg (1974, 1977), Boyer (1997), Walker et al. (1982), Abrahams et al. (1994); (b) metabolic pathways and regulation by Ochoa and Valdecasas (1929), Krebs and Johnson (1937), Novelli and Lipmann (1947), Fischer et al. (1959), Cori and Cori (1923, 1925), Houssay (1945, 1948), Lehninger (1942, 1945), Caputto et al. (1949), Cardini et al. (1950), Mitchell (1961), Benson and Calvin (1947), Hershko et al. (1980), Hershko and Ciechanover (1992), and (c) contributing to innovative techniques or approaches dedicated to advance basic knowledge (and making our lives easier) with Smith (1982), Winter et al. (1982), Mullis et al. (1986) (ante and post-PCR era) and Shimomura (1979), Chalfie et al. (1994), Heim et al. (1994) (ante and post-green fluorescent protein), Yalow et al. (1964), and Williams et al. (1977), Springer et al. (1979); (d) signaling molecules and signal transduction by Levi-Montalcini and Amprino (1947), Cohen et al. (1954), Sibley et al. (1986), Benovic et al. (1987), Frielle et al. (1987), Fargin et al. (1988). Back in 1896, Buchner's preparation of a “juice” from yeast (Buchner, 1897) is often regarded as the birth of modern biochemistry. However, I tend to digress with this strict view of biochemistry, reasoning that we (as a species) were taking advantage of biochemical principles without having a deep understanding of the underlying molecular processes. For instance, consider Buchner's “juice” or actually wine making. This method, that has at its core the fermentation process one of the key pathways in biochemistry, dating back to around 6000 BC (Chambers and Pretorius, 2010). Refer to the complicated production of fish sauces considered among the most common flavor-enhancing condiments produced and distributed across ancient Roman Empire (Lowe, 2009). Another example comes from the mixture of organic preservatives (i.e., biochemical) used for ancient Egyptian mummification (Buckley and Evershed, 2001). Or think about the effects of diet on health as recognized by Hippocrates (460–377 BC; Caramia, 2006), the arab physician Ibn al-Nafis (Al-Nafis, 13th century) and Leonardo da Vinci (1452–1519; Caramia, 2006) as well as the experimentation with animals and structure—function of human body set by the Medieval Islamic era as early as the 9th century (Abdel-Halim, 2011). This early biochemistry was empirical, done in settings other than laboratories, serving immediate needs, and some passed onto next generations by oral traditions. Then we would reason, are these contributions valuable to the genesis of biochemistry? Should they be dismissed because the microorganisms were not genotyped, the reactions were done in dolia instead of microplates? Then, if we accept these very early facts (and why not experiments?) as part of the genesis of this field, we will need to accept that biochemistry is a long, long (ancient?) journey that has accompanied us since the dawn of civilization. The general field of Biochemistry has grown since then to the point that it has been expanded to various more specific areas of research. For example, Cellular Biochemistry is at the crossroads of Chemistry (Organic, Physical, Analytical, Inorganic, Biological) and Biology (Chemical, Molecular) including studies on biomolecular structures and the mechanism of biochemical reactions, but also on the biological purposes of biochemical phenomena, i.e., metabolic pathways and their control, physiological significance and clinical relevance of topics presented. The regulation includes protein and gene expression analyses as well as protein post-translational modifications, epigenetic controls, metabolite-control systems, and gene-environment interactions as well as cell-cell interactions. This field covers areas from fundamental biochemical principles (e.g., enzymology, macromolecule structures) in cell-free systems to pathways, their regulation, and integration in physiology, and how their disturbance could lead to a number of diseases. While tremendous progress has been achieved, here are some of the aspects that we think needs additional attention in the next upcoming years.