Bioinformatics

VALERIO FULCI
CARLO COGONI

Students acquire the knowledge and thinking skills necessary to understand biological problems in a evolutionary perspective. The course will provide students with understanding of the basic molecular mechanisms that operate in living cells, with a focus on the flow of genetic information.

Detailed knowledge and full comprehension of the theory of evolution.
By the end of the course, students are expected to have attained a good knowledge of the structure and organization of prokaryotic and eukaryotic cells and of the general principles of transport across biological membranes.
Students shall show a detailed comprehension of the following biological processes: Flow of the genetic information (DNA replication, transcription, translation) gene expression regulation, cell respiration, photosynthesis, protein trafficking, secretion, exocytosis, endocytosis, signal transduction, cell cycle progression and mitosis.
Students shall be able to describe the structure, the function and the links between structure and function of the following cytoplasmic organelles: mitochondria, chloroplasts, endoplasmic reticulum, Golgi apparatus, lysosomes. Students shall also be able to discuss the major components of the cytoskeleton (microtubules, intermediate filaments, actin filaments) and of the extracellular matrix.
Students shall be able to discuss and comment on the cell cycle phases, mitosis, proto-oncogenes and tumor suppressor genes function, the molecular bases and the clonal evolution dynamics underlying cancer development.

Knowledge of basic principles of Chemistry is required

1. Definition of life. Darwinian evolution: variation, heredity and fitness. Gene-centered view of evolution: replicators and vehicles. Origin of life: pre-biotic chemistry, RNA world. From molecules to the first cells. Prokaryotes, Eukaryotes. From single cells to multicellular organisms. Mutualistic symbiosis and complexity. Microscopy: light microscopy, fluorescence microscopy, confocal microscopy, electron microscopy.
2. Proteins: structure and functions. Enzymes and biological reactions. Endergonic and exergonic reactions. Coupled reactions. Energy carriers: ATP, NADH, NADPH.
3. Bio-membranes: Structural Organization and Functions. Phospholipids and membrane proteins. Principles of membrane transport: active/passive transport, carrier proteins, ion channels, electro-chemical properties of membranes.
4. Energy for cellular activities. Production of ATP. Structure and function of mitochondria. Glycolysis, Krebs cycle, electron transport chain. The mitochondrial ATP synthase, oxidative phosphorylation. Fermentation. Structure and function of Chloroplasts. Photosynthesis: photosystems, light reactions, dark reactions, Calvin cycle.
5. Nucleotides, RNA and DNA structures. DNA replication: replication origins, enzymes, proofreading activity of DNA polymerases. Leading strand and lagging strand. Brief introduction to DNA damage and repair. The cell nucleus and its organization. The nucleolus. Chromatin structure: histones, nucleosomes. Brief introduction to epigenetic modifications.
6. Transcription and translation. RNA transcription in prokaryotes. mRNA transcription and processing in eukaryotes. Brief introduction to splicing. tRNA, rRNA. tRNA activation. The genetic code. Protein synthesis: initiation, elongation and termination.
7. Regulation of gene expression. Control of transcription in prokaryotes: bacterial operons. Control of transcription in eukaryotes. Post-transcriptional and translational regulation. Non-coding RNAs, microRNAs.
11. Principles of cell signaling: G Protein–Coupled Receptors. Effectors and second messengers. Receptor Tyrosine Kinases, MAP Kinase Pathways. Steroid hormones receptors.
8. The genome and it evolution. Circular DNA and eukaryotic chromosomes. Repetitive DNA. brief introduction to gene duplication, gene families, pseudogenes.
9. Endomembrane system: endoplasmic reticulum, Golgi apparatus. Protein sorting to subcellular compartments. Post-translational modifications: phsphorylation, methylation, acetylation, ubiquitination and glycosylation. Brief introduction to peroxisomes. Endocytic pathways: pinocytosys, endocytosis, phagocytosis. Lysosomes. Autophagy. Exocytic pathways: controlled and costitutive secretion.
10. The cytoskeleton: microtubules, actin filaments, intermediate filaments. Dynamic instability of microtubules, centrosomes, centrioles, flagella and cilia. Prokaryotic flagella. Threadmilling of actin filaments. Vesicle trafficking and motor proteins. Extracellular matrix, connective tissue, epithelia. Epithelial to mesenchimal transition. Cell movements and adhesion.
12. Eukaryotic cell cycle. Cyclin-dependent protein kinases (CdKs). Cell cycle checkpoints. G1, G2, S and M phases of cell cycle. Mitosis. Cytokinesis. Apoptosis: caspases activation through intrinsic and extrinsic signalling.
13. Genetics of cancer. The hallmarks of cancer. Oncogenes and tumor suppressor genes. Gain of function and Loss of function mutations.Ras, p53, retinoblastoma. Somatic evolution in cancer.

Alberts et al, Essential cell Biology, 6th edition W.W. Norton.

Taught classes during which the students are encouraged to ask questions or further insights on specific topics.
Exercises consisting in the development of simple python scripts to mimic key biological process (e.g. transcription, translation)

In person. Attendance of classes is not mandatory, yet highly recommended.

During the course the students will be encouraged to undertake informal in itinere assessments (whose results will not be taken into account for the final marks) aiming to help the student in identifying those topics in which their preparation is poor.
In itinere assessments will consist in multiple choice questions.

The final mark will be assessed through a written exam. Exams will start in June (after the end of the lessons of module II) and the dates will be timely published on Infostud website.
The written exam will consist in 31 multiple choice questions on the topics listed in the syllabus. Exam questions will be comparable to the questions which make up the in itinere assessments and aim to evaluate:
1) Knowledge and comprehension of the sepcific terminology of Biology
2) Comprehension of the chemical, molecular and evolutionary bases of biological processes
3) ability to put in the cell context biological processes
4) Problem solving capability in the context of cell biology.

Questions on any of the topics in the course syllabus are asked with comparable frequency.