C8496 - Mechanisms of Signaling and Molecular Interactions

Learning outcomes

Upon completion of the course, students will possess a solid understanding of the molecular mechanisms and structural and functional interactions that regulate intracellular signaling, processes essential for maintaining cellular homeostasis. They will also acquire skills in experimental methodologies for studying signaling processes, with a particular focus on the large-scale analysis of protein-protein interactions (PPIs), which represent the physical-functional basis of intracellular communication networks. Upon completion of the course, students: ii) understand the main cellular signaling pathways, their functional interconnections, and their regulatory mechanisms; ii) understand and are able to use computational resources and bioinformatics tools to analyze signaling pathways and molecular interaction networks; are skilled in identifying relevant molecular targets and understanding how they are regulated in different biological contexts, including major pathological states.

Course contents

The course is organized into two complementary modules:

Module 1 (3 ECTS credits – 21 hours): based on classroom lectures.

Module 2 (1 ECTS credit – 7 hours of lectures + 2 ECTS credits – 26 hours of computational laboratory sessions): based on classroom lectures integrated with computational laboratory activities.

Module 1

Lectures provide an integrated view of the molecular mechanisms governing intracellular signaling, emphasizing the functional interplay among signaling pathways, the role of mitochondria as signaling organelles, and the pharmacological relevance of signaling networks as therapeutic targets in human diseases. In particular, the topics covered will include:

Fundamental Mechanisms and Their Relevance in Pharmacological Targeting: i) cell signaling features; ii) molecular switches; iii) molecular signature of the GPCRs and RTKs; interaction and functional integration between GPCRs and RTKs receptors; iii) mechano-signaling; iv) structural organization and function of major cellular signaling effectors; v) second messengers and in vivo determination; vi) scaffold/adaptor proteins; vii) desensitization/endocytosis and cellular signaling.

Mitochondria in signal transduction and its role in the improvement of pharmacological targeting strategies: i) ultrastructure versus network organization; ii) OXPHOS system organization; ii) mitochondria as a cellular signaling platform; iii) signaling between mitochondria and ER; iv) ultrastructural features of the subcellular compartment MAMs and them contribute to biochemical process and signaling.

AMPK and mTOR signaling pathways and pharmacological modulation in diseases: i) AMPK and mTOR complexes: structure and cellular functions; ii) signaling mediated by the molecular complexes mTORC1 and mTORC2; iii) molecular interaction between AMPK and AKT in signaling triggered by amino acids and growth factors; iv) Autophagy as molecular and cellular axis regulated by the interplay between mTOR and AMPK to maintain cellular homeostasis.

Module 2

Laboratory module, which combines introductory lectures on computational methodologies with hands-on training in the use of bioinformatics tools will cover the following topics:

• General features and types of protein-protein interactions.
• Overview of methods for the determination of protein-protein interactions.
• Databases of protein-protein interactions, metabolic pathways and signaling pathways.
• Structural analysis of domains mediating protein-protein interactions through molecular graphics software (Bioinformatics Lab).
• Analyses of biological networks (Bioinformatics Lab).

Readings/Bibliography

Module 1

Required and Supplementary Bibliographic References

During the course, students will be provided with the laboratory activity protocol and a selection of original research articles and review papers chosen to expand upon the topics covered in class and to foster the development of critical scientific literature analysis skills. All teaching materials will be made available in PDF format through the University of Bologna's Virtual Learning Environment (https://virtuale.unibo.it [https://virtuale.unibo.it/] ).

Recommended References

To reinforce fundamental knowledge and further explore the core concepts of cellular and structural biochemistry, students are encouraged to consult the following textbooks:

• Cells – Lewin et al.
• Protein Structure and Function – Petsko & Ringe.
• Lehninger Principles of Biochemistry – Nelson & Cox.

Module 2

Articles and reviews will be provided during the lessons, provided in PDF format, undisclosed, and will be available to students on Virtual Learning Environment (https://virtuale.unibo.it [https://virtuale.unibo.it/] ).

Teaching methods

Module 1: The course is delivered through classroom lectures using PowerPoint presentations.

Module 2: The course is delivered through classroom lectures using PowerPoint presentations and exercises of databases search, molecular graphics (Chimera) and biological network analyses (Cytoscape). Softwares are freely downloadable and run on Windows, MacOS and Linux.

Although attendance at lectures is not compulsory, it is strongly recommended, as the course content will be presented by the instructor and discussed interactively with the class. This teaching approach is designed to facilitate learning and to support students in achieving the knowledge and skills defined in the course learning outcomes.

As concerns the teaching methods of this course unit, all students (including all the international incoming exchange students, i.e. ERASMUS) must attend Module 1, 2 online [https://www.unibo.it/it/servizi-e-opportunita/salute-e-assistenza/salute-e-sicurezza/sicurezza-e-salute-nei-luoghi-di-studio-e-tirocinio], while Module 3 on health and safety is to be attended in class. Information about Module 3 attendance schedule is available on the website of your degree programme ("studiare"--"formazione obbligatoria su sicurezza e salute").

Assessment methods

Assessment for Modules 1 and 2 is conducted jointly: students take the examinations for both modules on the same day and during the same examination session.

The final grade is calculated as the weighted average of the grades obtained in the two modules that make up the course. Students have the right to reject the proposed positive grade once (in accordance with the University Teaching Regulations, ART.16, paragraph 5).

Artificial Intelligence (AI) tools can be useful in supporting individual study with in-depth insights, summaries, and self-assessment pathways. Regarding the assessment of learning, during in-person exams the use of AI is prohibited. Any use constitutes a violation of academic integrity.

Module 1

Assessment of the learning outcomes will consist of an oral examination comprising 3–4 questions. The examination is designed to assess students' knowledge and understanding of the topics covered during the lectures and evaluate students' ability to integrate and relate the different topics addressed throughout the course, critically interpret experimental results, and demonstrate appropriate use of scientific and technical terminology. Attention will be paid to the clarity, accuracy, and rigor of the student's oral presentation.

Module 2

Assessment will be conducted orally, based on a presentation of a project prepared by the student on one or more proteins assigned in advance by the instructor at the conclusion of the laboratory sessions.

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 ) 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, considering the teaching objectives.

Students recognized as “working students”: please consult the dedicated website (https://www.unibo.it/en/study/guide-to-choosing-your-programme/balancing-study-and-work) to apply for this status and to learn about the available measures.

To obtain a final grade of 30/30 with honors, the student must show to know in depth all the topics covered during the lessons. Further, the student must explain and integrate the topics with properties of scientific language. To obtain a final grade of 30/30, the student must explain contents covered during the lessons and show the ability to properly integrate them with properties of scientific language. The final grade will be scaled from 30/30 to 18/30 based on the number of questions to which the student is able to answer and on her/his ability to integrate the topics with properties of scientific language. To obtain the minimum grade of 18/30 the student must show to have basic knowledge of all the content discussed during the lessons and not be able to integrate them with properties of scientific language.

Teaching tools

Module 1

The content of both the lectures and the laboratory activities will be presented using PowerPoint slides, supplemented with diagrams, figures, graphs, scientific articles, and other teaching materials. All course materials will be made available to students in digital format through the Virtual Learning Environment (https://virtuale.unibo.it). During lectures, the instructor may also use the whiteboard and other multimedia resources to facilitate students' understanding of the topics covered.

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 ) 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, considering the teaching objectives.

Module 2

The presentations used during the lessons and the scientific publications used for their preparation will be available on Virtual Learning Environment (https://virtuale.unibo.it). There will also be self-assessment tests in true/false format on Virtual Learning Environment (https://virtuale.unibo.it) (Module 2).

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) 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, considering the teaching objectives.

Office hours

See the website of Anna Maria Porcelli

See the website of Luisa Iommarini