90926 - EMERGING MOLECULAR BIOLOGY IN HEALTH AND DISEASE

Course Unit Page

Academic Year 2020/2021

Learning outcomes

Describe general overviews on stem cell biology Identify the most important solutions and problems arising from some of the most advanced views in cellular signaling, genome function and cellular reprogramming. Identify when progression in basic and translational research can effectively match unmet clinical needs Discuss the mechanisms underlying cell growth and differentiation, with particular reference to the modulation of gene expression, epigenetics, nuclear dynamics and signaling. Critically explain the future perspectives in Regenerative and Precision Medicine. Evaluate the most updated publications within the context of Molecular and Cellular Biology, with particular emphasis to mechanisms underlying cellular commitment and adaptation, reprogramming, and differentiation.

Course contents

The Course of EMERGING MOLECULAR BIOLOGY IN HEALTH AND DISEASE is divided into a total of 24 lessons.The topics covered for each lesson are shown below. The description of these topics also intends to provide an indication of the contribution of each lesson to the knowledge and skills to be achieved, as it is underlined in the Biomedical Implications. 

  1. Presentation of the Teacher and the Course. Introduction to the rationale and purpose of the covered topics. Illustration of the program. Critical discussion with Students of their background (in relation to the program) and expected outcomes. Discussion of learning and exam modalities. Proposal for Students to be involved in the development of two seminars, managed by them, chosen by taking a cue from the covered topics.
  2. Analysis of the physical dynamics of cellular microtubules. Microtubules are entities capable of mechanical and electromagnetic oscillations. Methods for studying the oscillations of microtubules at the nanomechanical and electromagnetic level: atomic force microscopy (AFM) and hyperspectral imaging (HSI). Biomedical implications: Microtubules in the generation of biophysical signals.
  3. Microtubules as a network of oscillators capable of synchronization and coordinated migration (swarming). The dynamics of microtubules in biomolecular recognition processes. Biomedical implications: Microbutules behave like a bioelectronic circuit capable of generating information.
  4. Microtubules and the new frontiers of mechanobiology. The "memory switching" properties inherent in individual microtubules. Dynamics of self-assembly of tubulin and three-dimensional visualization of microtubular electrical conductivity by means of tunneling microscopy (Scanning Tunneling Microscopy - STM). Microtubules as a new form of aquaporin. Biomedical implications: The microtubules and the cytoskeleton as a bioelectronic circuit capable of memory and intercellular connectivity.
  5. Chronobiology and rhythmic oscillations at the cellular level. From microtubule oscillations to rhythmic intracellular calcium oscillations. The endoplasmic reticulum, the Inositol-triphosphate (IP3) / Inositol-tetraphosphate (IP4) system, and the receptors for Ryanodine in the generation of cytoplasmic oscillations of calcium. Biomedical implications: Circadian rhythms are also sustained on a cellular and molecular level. The rhythmic oscillations of intracellular calcium seen as a digitized input for the generation of molecular signals.
  6.  Introductory notes on the use of physical energies in the modulation of cellular fate. Mechanical vibrations, shock waves, electromagnetic fields, photobiomodulation. Biomedical implications: premises for the reprogramming of stem and somatic cells using physical energies. New approaches in Regenerative and Precision Medicine.
  7. Nuclear trafficking of molecular signals. The nuclear pore complex. RAN-TC and Karyopherins. The nuclear import of transcription factors and protein kinases: prelude to epigenetic regulation, chromatin and gene transcription remodeling. Biomedical implications: The nucleus as a "portal" for the integration of essential biophysical signals in the regulation of cell biology.
  8. Nuclear receptors and signals. The "Intracrine" modality of cellular regulation. Correlation with endocrine, paracrine, and autocrine mechanisms. Implications of intracrine dynamics in the regulation of cell growth and differentiation. Biomedical implications: the intracrine world in cellular homeostasis and in the onset of pathological conditions (degenerative diseases, cancer).
  9. The world of exosomes. The nanovesicle factory. Differences from microvesicles. Exosomes as a shuttle of transcription factors, miRNA, Long-chian RNA and DNA. The concept of "one component - multiple targets" linked to the intracrine signaling of exosomes. Analysis of the physical structures of exosomes by AFM. Biomedical implications: exosomes as carriers of information pockets in intercellular communication. Debunking a dogma: making peptide trafficking possible through cell membranes.
  10. The intracrine world in the regulation of stem cell biology. Endorphins, intracrine modulation, and cardiogenesis. Mixed esters of hyaluronic acid with butyric and retinoic acids (HBR). The first synthetic intracrine. Biomedical implications: synthesis of molecules with differentiating and intracrine logics for new approaches of cardiovascular regenerative medicine.
  11. The Hedgehog system. A molecular signaling pathway intimately connected to the physical dynamics of microtubules and the nuclear trafficking of molecular signals. Hedgehog signaling and the primary cilium. Physical dynamics of the primary cilium: a cellular GPS that guides the orientation and polarity of somatic and stem cells during embryogenesis and tissue repair. Biomedical implications: Hedgehog, a system preserved from amphibians to humans, usable for activating myocardial regeneration in adult mammals.
  12. The Hippo Pathway and YAP/TAZ: a system harboring the constant exchange between endogenous chemical and physical stimuli for the regulation of cellular homeostasis. Convergence on the Hippo Pathway and YAP/TAZ of miRNAs that induce cardiac regeneration. The Hippo Pathway and YAP/TAZ system promote cardiac differentiation of stem cells by acting as a physical sensor for the nanostructure and nanomechanics of the intracellular environment. Biomedical implications: Hippo Pathway and YAP/TAZ are becoming the target of physical energies (mechanical and electromagnetic) to promote and guide stem differentiation and tissue regeneration.
  13. Transcriptional regulation. Physical remodeling of chromatin: DNA bending and DNA loops to guide the movement and sliding speed of the RNA polymerase complex. Transcription factors: Zinc Fingers, Nuclear Hormone Receptors (NHR), Homeodomains, and Leucine Zippers. Implications in the differentiation and maintenance of cell identity. Phosphorylation of transcription factors and their nuclear import. Transcription factors act as actuators of mechanical forces inside the transcriptional machinery. Biomedical implications: the nanomechanics of transcriptional processes is one of the new frontiers of epigenetic regulation and regenerative medicine.
  14. Wide-ranging transcriptional profiling. DNA microarrays. Serial Analysis of Gene Expression (SAGE). Biomedical implications: large-scale transcriptional analyses offer the opportunity to understand mechanisms involved in complex physiological events, such as stem cell differentiation, and tissue regeneration, as well as normal and pathological cell growth.
  15. The stromal-vascular niche: a nanotopography where chemical and physical signals come together to modulate the biology of stem cells. Use of weak mechanical forces for the processing of autologous adipose tissue into micro-fragmented preparations capable of preserving the stem component within the context of an intact stromal-vascular niche. Biomedical implications: development of adipose tissue derivatives ready for autologous use in regenerative medicine. Our experience in orthopedic, vascular, and dental regenerative medicine.
  16. Use of ad hoc conveyed radioelectric fields for the modulation of stem cell fate. Our experience in regenerative medicine: from the reversibility of the stem senescence process, to the induction of cardiogenesis, neurogenesis, vasculogenesis and skeletal myogenesis. Use of electromagnetic fields in the direct reprogramming of human adult somatic cells. Biomedical implications: Part A - Use of physical energies for in situ reprogramming of stem cells, and the development of a regenerative medicine without cell and tissue transplantation.
  17. Use of subsonic and acoustic mechanical vibrations for the modulation of the differentiating potential of human adult stem cells. Our experience in deciphering vibrational nanomechanical patterns by Atomic Force Microscopy (AFM) and Hyperspectral Imaging (HSI) in stem cells, and developing mechanical actuators to induce specific stem cell differentiation. Biomedical implications: Part B - Use of physical energies for in situ reprogramming of stem cells, and the development of a regenerative medicine without cell and tissue transplantation.
  18. Use of Shock Waves in the modulation of stem cell differentiation in vitro, and in the repair of damaged tissues in vivo. Clinical experience in the orthopedic field (bone and cartilage regeneration,  and complete repair of non-healing fractures), in heart failure, and peripheral ischemia. Biomedical implications: Part C - Use of physical energies for the in situ reprogramming of stem cells, and the development of a regenerative medicine without cell and tissue transplantation.
  19. Photobiomodulation. Chromophores, and Opsin-Like Molecules: recently discovered elements involved in the transduction of the molecular signals, in morphogenetic processes, and tissue self-healing. Scientific evidence in vitro and in vivo. Experience in animal models of cerebrovascular damage, traumatic or secondary to neurodegenerative pathologies, heart failure, and spinal cord injury. Use of Photobiomodulation as an advanced diagnostic alternative. Biomedical implications: Part D - Use of physical energies for in situ reprogramming of stem cells, and the development of a regenerative medicine without cell and tissue transplantation.
  20. Nano- and micro-electronic circuits in the treatment of irreversible spinal cord injuries. The support of new sensors and artificial intelligence. Biomedical implications: towards the creation of human-machine hybrids in regenerative medicine: perspectives and fears.
  21. The current legislation on the development and clinical applications of tissue repair strategies, regenerative medicine and precision medicine. European and US regulations compared. The concepts of Advanced Therapy Medicinal Products (ATMPs), current Good Manufacturing Practice (cGMP), Cell Factories and Biobanks. Biomedical implications: Regenerative Medicine and the need to fill an information gap, often also among professionals: knowing the current European and ExtraEuropean regulations that dictate how to apply regenerative medicine strategies to the human beings.
  22. The First Seminar conducted by groups of Students on issues selected by taking a glimpse from topics covered throughout the Course. The Teacher will intervene at the end of the seminar, to develop a collegial critical discussion of the work done by the Students.
  23. The Second Seminar conducted by groups of Students on issues selected by taking a glimpse from topics covered throughout the Course. The Teacher will intervene at the end of the seminar, to develop a collegial critical discussion of the work done by the Students.
  24. End of the Course. Final discussion and remarks. Clarification on the covered topics.

Readings/Bibliography

Readings and bibliography will be provided throughout the Course, during each lesson, stored and made available in the IOL section.

Teaching methods

  • Computer assisted presentations.
  • Discussion of experimental findings.
  • Seminars, particularly focused on novel approaches in Regenerative Medicine.
  • Presentation and discussion of main findings and major conclusions from International Meetings coherent with the aim, contents and outcomes of the Course.

Assessment methods

  • Computer assisted presentations.
  • Discussion at the end of each lesson.
  • Discussion of experimental findings.
  • Questions and highlights.
  • Seminars, particularly focused on novel approaches in Regenerative Medicine.
  • The final exam will focus on topics covered during the lessons, and will include a computer presentation of a short paper, arranged by the candidate, in suitable format (PPTX, Keynote, pdf).

Teaching tools

  • Power point presentations.
  • Critical discussion of personal research and review articles.
  • Critical readings of studies published by other Authors.
  • Presentation of movies form international meetings.

Office hours

See the website of Carlo Ventura