90926 - Emerging Molecular Biology in Health and Disease

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

Foundations of biomedical research and molecular biology

- The scientific method in biomedical research. The scientific method: observation, hypothesis, experimentation, data analysis, and theory building. Experimental design and reproducibility. Controls, bias, and statistical significance. Translational research pipeline: from basic discovery to clinical application.

- Types, structure and critical evaluation of a scientific articles. Types of scientific articles. Scientific original article sections: abstract, introduction, methods, results, discussion. The peer review process. Journal impact factors. How to search for scientific papers.

- DNA Structure, function and regulation: from discovery to modern concepts. The identification of DNA as the hereditary material. The discovery of the double helix and base-pairing rules. The establishment of the central dogma of molecular biology. DNA manipulation and the birth of biotechnology. Gene regulation, genomics, and new technologies. Precision and systems biology. 

 

Embryonic and induced pluripotent stem cells, gene editing and molecular tools for constitutive, transient and time-controlled gene expression

- Embryonic stem cells and induced pluripotent stem cells. Embryonic and adult stem cells: potency and differentiation. Role of transcription factors in lineage commitment and differentiation. Reprogramming somatic cells to induced pluripotent stem cells (iPS)

- Conventional and conditional gene editing. Non-homologous and homologous recombination. Genetic Engineering of model organisms. Conventional knock-out strategies. DNA recombinases. Cre-Lox system for tissue-specific knock-out and knock-in. Application examples in different organs.

- Molecular tools for constitutive, transient and time-controlled gene expression. Basic principles of gene expression control. Viral vectors. emerging RNA-based therapeutics (including modified mRNA). Tet-OFF/Tet-ON systems for inducible, tissue-specific, and time-controlled gene expression.

 

Tissue renewal, adult stem cells and their application as regenerative therapies. 

- Tissue renewal and its analysis: cell cycle, proliferation and cellular sources. Renewal capacities across tissues and organs. Overview of the cell cycle, checkpoints and regulation. Methods for measuring proliferation, including Ki67, PCNA and phospho-H3 analysis, and BrdU/EdU incorporation assays. Determining sources of regeneration via lineage tracing.

- Highly proliferative tissues: bone marrow stem cells and therapeutic applications. Hematopoietic and mesenchymal stem cells. Hematopoietic stem cell niches and regulatory mechanisms. Hematopoietic stem cell mobilization. Clinical applications of stem cell transplantation and regenerative therapies.

- Highly proliferative tissues: skin, cornea, and intestine. Stem cell niches, renewal dynamics, and regenerative therapies in epithelial tissues.

- Quiescent stem cells in skeletal muscle. Satellite cells in muscle repair. Activation mechanisms and therapeutic potential.

- Slowly proliferating tissues: neural stem cells and brain renewal. Evaluation of brain tissue renewal with 14C incorporation. Neural stem cells during brain development and adult neurogenesis. Brain neurogenic niches in adult individuals. Preclinical and clinical studies for neuronal regeneration: lessons learned so far.

- Slowly proliferating tissues: the cardiac tissue. Evaluation of heart tissue renewal with 14C incorporation. Clinical trials for cardiac regeneration based on adult stem cells. Cardiac progenitors during prenatal development. Controversies on adult cardiac stem cells and the emerging consensus based on lineage tracing. Discussion of the failure of adult stem cell therapies for cardiac regeneration.

- Liver Stem Cells and Regeneration. Role of liver stem and mature cells in regeneration and clinical implications.

- Stem/progenitor cells in other organs (kidney, lung, and pancreas..). Overview of regenerative potential and emerging therapeutic applications.

 

Cellular plasticity and alternative regenerative strategies.

- Regeneration capabilities across species: lessons for human biology. Comparative analysis of regenerative mechanisms in model organisms and implications for human therapies.

- Mature cell dedifferentiation: molecular mechanisms and therapeutic potential. Markers and features of dedifferentiation. Signaling pathways involved. Role in tissue regeneration.

- Transplantation of IPS-derived differentiated cells, and transdifferentiation as regenerative strategies. Differentiation of iPS and embryonic stem cells (ES) in vitro and transplantation in vivo. Direct reprogramming (transdifferentiation) of somatic cells into specific cell types. Applications in regenerative medicine.

- Therapeutic technologies for gene expression control. Emerging technologies for controlling gene expression in humans, including tunable viral vectors.

 

Student-Led Discussions and Presentations

- Presentation and critical discussion of recent publications in molecular biology and regenerative medicine. Students present and critically analyze research articles focusing on molecular mechanisms of cellular commitment, adaptation, reprogramming, and differentiation. Group discussions to evaluate translational potential and clinical relevance in regenerative and precision medicine.

Readings/Bibliography

All teaching materials presented during the lectures will be made available to students through the Virtual Learning Environment platform [https://virtuale.unibo.it/ ].

For further study, students are free to use any Molecular Biology textbook, in either Italian or English. By way of example, the following volumes are recommended:

Iwasa and Marshall – Karp’s Cell and Molecular Biology: Concepts and Experiments – Ninth Edition 

Krebs et al. - Lewin's Essential GENES

Krebs et al. - Lewin's GENES XII

Clark et al - Molecular Biology

Lodish et al - Molecular Cell Biology

Watson et al. - Molecular biology of the gene

Albert et al. - Molecular Biology Of The Cell

Teaching methods

• Frontal lessons through computer-assisted presentation and critical discussion of scientific articles.
• Tests at the end of the lessons will be used to support learning.
  

Attendance to this learning activity is mandatory; the minimum attendance requirement to be admitted to the final exam is 60% of lessons. Students who fail to meet the minimum attendance requirement will not be admitted to the final exam of the course and will have to attend relevant classes again during the next academic year. Professors may authorize excused absences upon receipt of proper justifying documentation, in case of illness or serious reasons. Excused absences do not count against a student’s attendance record to determine their minimum attendance requirement.

Assessment methods

The students will be evaluated by written exam.

The written test consists of 31 multiple-choice questions, with only one correct answer per question. Students will receive 1 point for each correct answer, and 0 points for incorrect or missing answers.

The time available to students for the written test is 30 minutes. During the test, the use of support materials, such as textbooks, notes, computer supports, is not allowed. The maximum score obtainable by providing all correct answers is equal to 30 cum laude. The test is considered passed with a minimum score of 18/30.

To improve their final grade of the written exam, students may opt for an oral exam. This consists of a brief presentation of a scientific article, followed by a critical discussion of the article itself and of topics addressed during the course.

⚠️ Please note that the final grade may be adjusted upward or downward based on the outcome of the oral exam.

Students with learning disorders and\or temporary or permanent disabilities: please, contact the office responsible (https://site. unibo.it/studenti-con- disabilita-e-dsa/en/for- students [https://site.unibo.it/studenti-con-disabilita-e-dsa/en/for-students] ) as soon as possible so that they can propose acceptable adjustments. The request for adaptation must be submitted in advance (15 days before the exam date) to the lecturer, who will assess the appropriateness of the adjustments, taking into account the teaching objectives.

Teaching tools

All educational materials presented will be available to students through Virtual Learning Environment portal [https://virtuale.unibo.it/] .

Office hours

See the website of Gabriele Matteo D'Uva