Molecular and systems biolology

Subject description

Molecular and systems biology are basic natural sciences, which are focused not only on microbial cells (archaea, bacteria, fungi, algae, protozoa), but also on animal and plant cells, on the level of molecular mechanisms, role and structure of different molecules and macromolecules, responses to different environmental impacts and consequential changes (regulation, transcription, translation and post translational modifications). Research is on one hand focused on studying normally functioning cells, and on the other hand in searching for malfunctions, which can cause diseases. This frame includes also the field of genomics and metagenomics, focused on either individual cells, microbial communities or tissues, as bearers of potentially and selectively expressed genetic information. Investigations therefore include the level of individual cells, acting as model organisms or the more complex level of communities and tissues.Because of the complexity of information, understanding requires an approaches that include modelling of biological systems and synthesis of aquired knowledge.

Within the framework of the subject, the participating lecturers will introduce students in more details to a selection of themes listed below:

1.Molecular basis of the programmed cell death in plants in comparison with other cells, both prokaryotic and eukaryotic;

2. Adaptations of extremophilic microorganisms to life in extreme environmental conditions (high or low temperatures, alcalic or acidic pH, high concentration of NaCl, high pressure or radiation) on the level of macromolecules (lipids, proteins, nucleic acids), in comparison with mesophilic homologues. Focus on therodynamic stability of listed biological molecules, with the main emphasis on thermodynamic and kinetic stability of proteins during folding and unfolding, role of misfolded proteins and amiloides in different diseases (Parkinson's disease and prionic diseases);

3. Learning about synthesis, processing, transport and turnover of RNA. Learning about the complex world of non-coding RNA molecules (microRNA, snoRNA and lncRNA) and their multilevel role in the expression of genes. Biological and disease related functions of different RNA families (mRNA, miRNA, snoRNA, siRNA).

Presentation of the regulatory networking of RNA, which is likely to have important impact on the complex characteristics of organisms, and plays an important role in development and disease states;

4.Comparison of structure-function relationship of clinically relevant enzymes (e.g. esterases)and the mechanism of action with inhibitors and their role in clinical treatment. Learning about modern enzymatic methods for the determination and analysis of kinetic parameters on large-scale data;;

5. Learning about tumors, with the description of characteristic molecular changes, as molecular targets for target drugs. Basics of cancer gene therapy and its usefuleness in treating different types of cancer;

6.Learning about genomics of microorganisms, with emphasis on general differences between the genomes of prokaryotes and eukaryotes, approaches to genome sequencing, methods of comparative genomics. Analyses made possible by modern bioinformatic tools in the fields of genomics and comparative genomics with illustration based on practical examples;

7.learning about post-genomic biology, new sequencing techniques, approaches in metagenomics, approaches in metatranscriptomics, single cell genomics, aquatic metagenomics, soil metagenomics, sediment metagenomics, human metagenomics, metavirioms, introduction to Linux, assembly and annotation of prokaryotic genomes, analysis of metagenomic libraries, assembly and annotation of metagenomic DNA;

8. Modelling in systems biology: knowledge bases used in molecular modelling, formalisms used in modelling of biological systems, tools available for structural and dynamic modelling and experimental data acquisition to support modelling.

9. Structure and functional asymmetry of biological membranes, lipid microdomains, protein-membrane interactions, modern techniques for studying artificial and biological membranes and their components.

The subject is taught in programs

Objectives and competences

Students will get deeper insight into the research area which he or she will upgrade in her/his doctoral thesis. The contents are not intended to extensively broaden theoretical knowledge, instead it should present specific problematic research areas and indicate methods and approaches which can facilitate solving of scientific problems. Student should get also familiar with previous research in the field of their doctoral thesis.

One of the aims is to mediate key scientific literature from the chosen scientific field, including mediation of the lecturer’s own experience and help in the analyses of experimentally obtained data.

Specific aims:

gain of special knowledge associated with archeal, bacterial, fungal, animal and plant cell,
learning about the physical laws that determine the stability of biological macromolecules at extreme environmental conditions,
learning about the complex world of non-coding RNA molecules ( microRNA, snoRNA and lncRNA) and their multilevel role in the expression of genes,
understanding the molecular mechanisms of clinically important peptides. Understanding that chemical modifications of natural peptides can change the biological activity of the native peptides and consequently lead to more efficient clinical therapy,
understanding the molecular mechanisms and interaction systems involved in biogenesis, transport, function and turnover of different families of RNA. To gain insight into disease significant processes and methods of treatment
understanding the basic characteristics of microbial genomes and methods for their analysis. Recognising the potentials for basic and applicable outcomes of genomic analyses and their limitations (what cannot (yet) be discerned on the basis of the genomic sequence).
gaining an in-depth insight into metagenomics and its research applications
familiarizing with the field of systems biology, including wet and dry lab methodologies.

Teaching and learning methods

Preparation and supervision of Journal clubs, discussion and consultation in relation to scientific problems with explanations, discussions, demonstrations, text work, informatics, research learning.

Describing a real-life research problem and the stages of its solving, with accompanying explanation of the relevant knowledge, important in the process.

Expected study results

Such an approach should result in the proper planning of research experiments which should enable testing of the hypotheses raised in the doctoral thesis,

familiarity with the chosen research area, capability to explain the main principles and interpretation of the obtained results.

Knowledge and understanding:

understanding of plant cell death programs in comparison with programs in animal and microbial cells,

understanding of macromolecular stabilisation of extremophiles,

understanding of regulatory networking of RNA, likely to have an important impact on the complex characteristics of organisms, and in development of different diseases,

understanding of the molecular mechanisms which enable peptides to exert their cell function and identification of peptides as clinically important molecules,

understandinging of dynamics of RNA synthesis and processing, as well as of the crucial functions of different families of RNAs,

understanding of characteristics of microbial genomes, of different (basic) approches for genomic sequence analysis and of different (basic) approches for genomic sequence comparison,

Understanding of importance of metagenomics and its use in different research fields,

acquirement of an overview of existing methodology in systems biology and the ability to identify the best methodlogical approach availabile for solving specific problems of biological systems modeling.

Basic sources and literature

Novejši znanstveni pregledni in eksperimentalni članki s področja, druga učna gradiva in spodaj navedene knjige ter pregledni članki.

Recent review scientific and experimental papers, literature from the field, text books, and books and review articles listed below.

Knjige/Books:

1. Bioinformatics: Sequence and Genome Analysis, 2nd edition, David W. Mount. Cold Spring Harbor Laboratory Press.

2. Edda Klipp , Wolfram Liebermeister , Christoph Wierling , Axel Kowald , Hans Lehrach , Ralf Herwig: Systems Biology, Wiley, 2009

3. Eberhard Voit A First Course in Systems Biology, Garland Science, 2012

4. Dermastia, Marina. Pogled v rastline. Ljubljana: Nacionalni inštitut za biologijo, 2010. 237 str., ilustr. ISBN 978-961-92543-4-9. pp 1-74.

4. Radiobiology for Radiologists. E Hall and Amato J. Gaccia, seventh edition, Wolters Kluwer and Lippincott, 2012The Basic Science of Oncology. Fofth edition, Tannock I, Hill R, Bristow R, Harrington L. Mc Graw Hill 2013

5. Thermophiles: Biology and technology at high temperatures, Ed. F. Robb, G. Antranikian, D. Grogan, A. Driessen (2008). CRC Press, pp. 7-73.

Članki/Papers:

Dinger ME. Long non-coding RNAS in disease and development. Pathology. 2014 Feb;46 Suppl 1:S26.
Uversky, V. (2011) Intrinsically disordered proteins from A to Z. International Journal of Biochemistry & Cell Biology 43, 1090-1103.

4. Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007 May;132(6):2131-57.

5. Zinman B. Newer insulin analogs: advances in basal insulin replacement. Diabetes Obes Metab 2013;15(Suppl. 1):6–10.

6. Bavec A (Poly)peptide-based therapy for diabetes mellitus: Insulins versus incretins. Life Sci. 2014 Jan 8. pii: S0024-3205(14)00005-8. doi: 10.1016/j.lfs.2013.12.210.

Strojan, Hočevar ured.: Onkologija [Elektronski vir] : učbenik za študente medicine, Ljubljana : Onkološki inštitut = Institute of Oncology, 2018, SBN – 978-961-7029-06-2; COBISS.SI-ID – 294451456; https://www.onko-i.si/fileadmin/onko/datoteke/Strokovna_knjiznica/publikacije_za_bolnike/Onkologija_ucbenik_za_studente_medicine_2018.pdf
Harrington L, Tannock I.F., Hill R.P., Cescon D. (2021). The Basic Science of Oncology. 6th ed. McGraw-Hill Professional. pp 558, ISBN: 978-1259862076.
Weinberg R.A. (2014). The Biology of Cancer. ISBN 978-0-8153-4219-9