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sbglab research molecules

Molecules of pharmacological interest

Medical control of cancer may greatly benefit from the pharmaceutical potential of natural-derived compounds. Insofar many natural products – originating from eggs, fruits, plants and herbs – display a diversified set of anticancer effects, interest in their clinical utilization has gained momentum during the last decades.

Our lab is especially involved in studying the pleiotropic, ‘systems’ effects of a few set of very promising molecules, such as Melatonin, Inositol and Protein extracts from embryo fish. These compounds have been demonstrated to target both cell as well as microenvironmental-linked pathways (apoptosis modulation, cell proliferation, redox balance, calcium release, and microtubule and microfilament reorganization).

It is worth of noting that these molecules specifically affects cytoskeleton configuration and function, and by that way they have been proved to influence the tri-dimensional pattern of cell-microenvironment cross-talk, especially during developmental processes, like those occurring during oocyte maturation, embryogenesis and cancer onset.

Molecules of pharmacological interest

sbglab research molecules

Medical control of cancer may greatly benefit from the pharmaceutical potential of natural-derived compounds. Insofar many natural products – originating from eggs, fruits, plants and herbs – display a diversified set of anticancer effects, interest in their clinical utilization has gained momentum during the last decades.

Our lab is especially involved in studying the pleiotropic, ‘systems’ effects of a few set of very promising molecules, such as Melatonin, Inositol and Protein extracts from embryo fish. These compounds have been demonstrated to target both cell as well as microenvironmental-linked pathways (apoptosis modulation, cell proliferation, redox balance, calcium release, and microtubule and microfilament reorganization).

It is worth of noting that these molecules specifically affects cytoskeleton configuration and function, and by that way they have been proved to influence the tri-dimensional pattern of cell-microenvironment cross-talk, especially during developmental processes, like those occurring during oocyte maturation, embryogenesis and cancer onset.

A different approach on cancer research

The Somatic Mutation Theory (SMT) of carcinogenesis encompasses significant inconsistencies. Indeed, the increasingly burden of unexplained paradoxes and shortfalls is driving the current carcinogenesis theory toward a blind alley.

Ignoring these paradoxes is unsustainable. By avoiding these conundrums, the scientific community is depriving itself of the opportunity to achieve real progress in this important biomedical field.

Environment-organism interaction: the epigenetic point of view.

What molecular mechanisms regulate cell senescence and organism aging? Why aging processes show different onset, duration and intensity in different subjects? Why the normal and healthy aging could deviate toward a pathological condition? Why so many diseases are age-related? The complexity of the aging processes makes it difficult to simply answer to these questions. Moreover a bias is added by the possibility that changes leading to pathological aging originate earlier in life and show a more or less “asymptomatic” period. Paradoxically, exactly these two features could suggest one possible answer: epigenetic modifications retain the ability to orchestrate complex processes that result in altered gene expression and can reveal the associated, pathological, phenotype even after many years. Moreover, epigenetic modifications can represent the effectors mediating the environmental insults that a subject encounters during his life.

A section of the Systems Biology Group lab carries on neuro-epigenetic studies with particular interest toward the role of DNA methylation in neurodegenerative processes. This line of the research, aimed at deciphering the complex interaction between environmental factors or natural compounds (such as S-adenosyl-methionine, vitamin K, inositol, alpha-lipoic acid, inositol) and DNA methylation, found its applicative fields not only in neurodegenerative models but virtually in all the experimental models studied in the lab.

Therefore, cancer research should be reframed by embracing new theoretical perspectives, taking the cells-microenvironment interplay as the privileged level of observation. This implies we have to adopt radically different premises as such provided by The Tissue Organization Field Theory (TOFT), according to which cancer arises as a consequence of altered cross-talk among cells and their microenvironment. In turn, modification in the cell-stroma interaction may efficiently modulate key phase-transition, thus promoting true tumor reversion.

However, experimental and clinical evidences suggest that cancers can be induced to become quiescent, differentiate, die or form completely normal tissues, if provided with the correct set of complex signals, as conveyed by embryonic tissues or other microenvironmental cues.

These data suggest that by manipulating cancer microenvironment may help in opening new avenues for therapeutic solutions.

Life in Space: an unexpected thoughtful model

Gravity has constantly influenced both physical and biological phenomena throughout Earth’s history. The gravitational field has played a major role in shaping evolution when life moved from water to land. However, gravity may influence in a more deep and subtle fashion the way the cells behave and build themselves. Cells may indeed ‘sense’ changes in the microgravity field through (1) an indirect mechanism (mainly based on the modification of physical properties of their microenvironment); (b) the development of specialized structures for the mechanical perception and transduction of gravitational forces (like the cytoskeleton); (c) changes in the dynamics of enzymes kinetics or protein network self-assembly. It is worth noting that the latter two processes are dramatically affected by non-equilibrium dynamics.

That prerequisite is needed in order to allow the system to promptly change its configuration, according to the system’s needs. In turn, the dissipative energy provides the thermodynamic driving force for the self-organization processes. Accordingly to some preliminary results, gravity seems to influence non-equilibrium processes (like the cytoskeleton reorganization), acting as an ‘inescapable’ constraint that obliges living beings to adopt only a few configurations among many others. By ‘removing’ the gravitational field, living structures are free to recover more degrees of freedom, thus acquiring new phenotypes and new functions/properties.

These data raise several crucial questions. Some of these entail fundamentals of theoretical biology, as they question the gene-centric paradigm, according to which biological behavior can be explained by solely genetic mechanisms. Indeed, influence of physical cues in biology (and, in particular, on gene expression) is still now largely overlooked. This is why it has been argued that the ultimate reason for human space exploration is precisely to enable us to discover ourselves. Undoubtedly, the microgravity space-field presents an unlimited horizon for investigation and discovery. Controlled studies conducted in microgravity can advance our knowledge, providing amazing insights into the biological mechanism underlying physiology as well as many relevant diseases, like cancer. Thereby, space-based investigations may serve as a novel paradigm for innovation in basic and applied science.

A different approach on cancer research

The Somatic Mutation Theory (SMT) of carcinogenesis encompasses significant inconsistencies. Indeed, the increasingly burden of unexplained paradoxes and shortfalls is driving the current carcinogenesis theory toward a blind alley.

Ignoring these paradoxes is unsustainable. By avoiding these conundrums, the scientific community is depriving itself of the opportunity to achieve real progress in this important biomedical field.

Environment-organism interaction: the epigenetic point of view.

What molecular mechanisms regulate cell senescence and organism aging? Why aging processes show different onset, duration and intensity in different subjects? Why the normal and healthy aging could deviate toward a pathological condition? Why so many diseases are age-related? The complexity of the aging processes makes it difficult to simply answer to these questions. Moreover a bias is added by the possibility that changes leading to pathological aging originate earlier in life and show a more or less “asymptomatic” period. Paradoxically, exactly these two features could suggest one possible answer: epigenetic modifications retain the ability to orchestrate complex processes that result in altered gene expression and can reveal the associated, pathological, phenotype even after many years. Moreover, epigenetic modifications can represent the effectors mediating the environmental insults that a subject encounters during his life.

A section of the Systems Biology Group lab carries on neuro-epigenetic studies with particular interest toward the role of DNA methylation in neurodegenerative processes. This line of the research, aimed at deciphering the complex interaction between environmental factors or natural compounds (such as S-adenosyl-methionine, vitamin K, inositol, alpha-lipoic acid, inositol) and DNA methylation, found its applicative fields not only in neurodegenerative models but virtually in all the experimental models studied in the lab.

Therefore, cancer research should be reframed by embracing new theoretical perspectives, taking the cells-microenvironment interplay as the privileged level of observation. This implies we have to adopt radically different premises as such provided by The Tissue Organization Field Theory (TOFT), according to which cancer arises as a consequence of altered cross-talk among cells and their microenvironment. In turn, modification in the cell-stroma interaction may efficiently modulate key phase-transition, thus promoting true tumor reversion.

However, experimental and clinical evidences suggest that cancers can be induced to become quiescent, differentiate, die or form completely normal tissues, if provided with the correct set of complex signals, as conveyed by embryonic tissues or other microenvironmental cues.

These data suggest that by manipulating cancer microenvironment may help in opening new avenues for therapeutic solutions.

Life in Space: an unexpected thoughtful model

Gravity has constantly influenced both physical and biological phenomena throughout Earth’s history. The gravitational field has played a major role in shaping evolution when life moved from water to land. However, gravity may influence in a more deep and subtle fashion the way the cells behave and build themselves. Cells may indeed ‘sense’ changes in the microgravity field through (1) an indirect mechanism (mainly based on the modification of physical properties of their microenvironment); (b) the development of specialized structures for the mechanical perception and transduction of gravitational forces (like the cytoskeleton); (c) changes in the dynamics of enzymes kinetics or protein network self-assembly. It is worth noting that the latter two processes are dramatically affected by non-equilibrium dynamics.

That prerequisite is needed in order to allow the system to promptly change its configuration, according to the system’s needs. In turn, the dissipative energy provides the thermodynamic driving force for the self-organization processes. Accordingly to some preliminary results, gravity seems to influence non-equilibrium processes (like the cytoskeleton reorganization), acting as an ‘inescapable’ constraint that obliges living beings to adopt only a few configurations among many others. By ‘removing’ the gravitational field, living structures are free to recover more degrees of freedom, thus acquiring new phenotypes and new functions/properties.

These data raise several crucial questions. Some of these entail fundamentals of theoretical biology, as they question the gene-centric paradigm, according to which biological behavior can be explained by solely genetic mechanisms. Indeed, influence of physical cues in biology (and, in particular, on gene expression) is still now largely overlooked. This is why it has been argued that the ultimate reason for human space exploration is precisely to enable us to discover ourselves. Undoubtedly, the microgravity space-field presents an unlimited horizon for investigation and discovery. Controlled studies conducted in microgravity can advance our knowledge, providing amazing insights into the biological mechanism underlying physiology as well as many relevant diseases, like cancer. Thereby, space-based investigations may serve as a novel paradigm for innovation in basic and applied science.