Učni načrt predmeta

Predmet:

Stabilnost, zvijanje in agregacija proteinov

Course:

Stability, Folding and Aggregation of Proteins

Študijski program in stopnja / Study programme and level	Študijska smer / Study field	Letnik / Academic year	Semester / Semester
Nanoznanosti in nanotehnologije, 3. stopnja	Bioznanosti	1	1
Nanosciences and nanotechnologies, 3rd cycle	Biosciences	1	1

Vrsta predmeta / Course type

Izbirni

Univerzitetna koda predmeta / University course code:

NANO3-834

Predavanja Lectures	Seminar Seminar	Vaje Tutorial	Klinične vaje work	Druge oblike študija	Samost. delo Individ. work	ECTS
30	30			30	21	10

*Navedena porazdelitev ur velja, če je vpisanih vsaj 15 študentov. Drugače se obseg izvedbe kontaktnih ur sorazmerno zmanjša in prenese v samostojno delo. / This distribution of hours is valid if at least 15 students are enrolled. Otherwise the contact hours are linearly reduced and transfered to individual work.

Nosilec predmeta / Course leader:

prof. dr. Eva Žerovnik

Sodelavci / Lecturers:

Jeziki / Languages:

Predavanja / Lectures:

Slovenščina, angleščina / Slovene, English

Vaje / Tutorial:

Pogoji za vključitev v delo oz. za opravljanje študijskih obveznosti:

Prerequisites:

Končan študij druge stopnje biokemije, biologije, medicine ali katerekoli druge naravoslovne smeri.

Second cycle degree in biochemistry, biology , medicine or any other natural sciences discipline.

Vsebina:

Content (Syllabus outline):

- Stabilnost proteinov: osnovna znanja o določanju stabilnosti,
- problem zvijanja proteinov - kako se proteini zvijajo in vitro in in vivo,
- kinetika, prehodna stanja in energije prehodov (energijske površine),
- kako se zvijanje začne - najzgodnejše stopnje,
- razrahljani klopčič (molten globule) - pomen zvijanje, napačno zvijanje in prehajanje preko membrane,
- encimi, ki sodelujejo pri procesih zvijanja,
- vloga šaperonov na zvijanje in vivo,
- agregacija proteinov do amiloidnih fibril: in vitro in v celici,
. reverzibilni kondenzati proteinov v telesca brez membran; podobnost s fazno separacijo gel- tekoče
- zvijanje proteinov in bolezni: nevrodegenerativne bolezni.

- Stability of proteins: basic knowledge of stability and its determination,
- The problem of protein folding - folding in vitro and in vivo,
- Kinetics, transition states and energy landscapes,
- How does folding start? - detecting the early stages,
- The molten globule - its relevance in folding, aggregation and protein translocation,
- The enzymology of protein folding,
- The role of chaperones in folding in vivo,
- Aggregation to amyloid-fibrils: in vitro and in the cell,
- Reversible condenstion of proteins into membrane-less bodies; similarity to gel-liquid phase separation
- Protein folding and disease; neurodegenerative diseases.

Temeljna literatura in viri / Readings:

Books:
Mechanisms of Protein Folding, 2nd edn., (2000) R. H. Pain (ed.), Oxford University Press.
Protein Folding-Misfolding: some current concepts of protein chemistry. Zbilut JP and Scheibel T (eds.), Nova Sci Publi., New York, 2007.
Protein misfolding diseases; current and emerging therapies. eds Raminez-Alvarado, J.W. Kelly, C.M. Dobson, Wiley Series in Protein and Peptide Science, Series Ed. V.N. Uversky. John Wiley & Sons, New Jersey 2010.

Selected papers:
Lion et al., 2021. A framework for understanding the functions of biomolecular condensates across scales. Nat Rev Mol Cell Biol, 2021 Mar;22(3):215-235. doi: 10.1038/s41580-020-00303-z.
ŽEROVNIK, Eva. Viroporins vs. other pore-forming proteins : what lessons can we take. Frontiers in chemistry, ISSN 2296-2646. [Online ed.], 2021, vol. 9, str. 626059-1-626059-6, doi: 10.3389/fchem.2021.626059.
issue: http://www.mdpi.com/journal/biomolecules/special_issues/protein-folding#published
Eichner T, Kalverda AP,. Thompson GS, Homans SW. and Radford SE (2011) Conformational Conversion during Amyloid Formation at Atomic Resolution. Molecular Cell 41: 161-172.
Sharma, S. et al. (2008). Monitoring protein conformation along the pathway of chaperone-assisted folding. Cell, 133,142-153.
Felitsky et al., (2008). Modeling transient collapsed states of an unfolded protein to provide insights into early folding events. Proc. Natl. Acad. Sci USA 105: 6278-6283.
Žerovnik E, Stoka V, Mirtič A, Gunčar G, Grdadolnik J, Staniforth RA, Turk D, Turk V. (2011). Mechanisms of amyloid fibril formation--focus on domain-swapping. FEBS J. 278:2263-82. doi: 10.1111/j.1742- 4658.2011.08149.x. Epub 2011 May 31. Review.
Di Scala e tal., (2016) Common molecular mechanism of amyloid pore formation by Alzheimer's b- amyloid peptide and a-synuclein Scien. Reports, DOI: 10.1038/srep28781.
Sengupta U, Nilson N.A., Kayed R., The role of amyloid-b oligomers in toxicity, propagation, and immunotherapy EBioMedicine , 2016, vol6, 42-49."""

Cilji in kompetence:

Objectives and competences:

Cilji: Študentje spoznajo osnove zvijanja proteinov in njihove stabilnosti. Pridobijo vpogled v termodinamske, kinetične in strukturne vidike procesa zvijanja. Nadalje se seznanijo s povezanim
mehanizmom agregacije proteinov. Ta se pojavlja
pri nevrodegenerativnih boleznih.

Kompetence: Spoznavanje z interdisciplinarnimi
področji strukturne biologije, biokemije in biofizike. Samostojno mišljenje, formuliranje problemov in vprašanj.

Objectives: To enable students to understand the
principles of protein folding and stability.
Thermodynamic, kinetic and structural aspects are
discussed. In addition, they become familiar with
the associated mechanisms of protein aggregation
which is involved in neurodegenerative diseases.

Competences: get to know interdisciplinary fields
of structural biology, biochemistry and biophysics.
Independent and creative thinking; be able to
formulate problems and open questions.

Predvideni študijski rezultati:

Intendeded learning outcomes:

Splošno
Študent bo spoznal:
- metode in procedure, ki se uporabljajo na
področju stabilnosti in zvijanja proteinov. Te
obsegajo razne biofizikalne in biokemijske
metode kot tudi razne spektroskopije, med
drugim fluorescenco, CD, NMR, FTIR,
- razvoj kritične in samokritične presoje,
- razvoj komunikacijskih sposobnosti in
predstavitve rezultatov raziskav,
- kooperativnost, delo v skupini,
- seznanil se bo z multidisciplinarnim pristopom k reševanju znanstvenih problemov.

Predmetnospecifična znanja:
- predmet pripravlja študente za delo na temeljnih raziskavah na področju predmeta,
- pridobljeno znanje pa je uporabno tudi v biotehnologiji in živilski tehnologiji,
- daje molekularne osnove za razumevanje nekaterih patologij – povezava z biomedicino.

General:
- The student will get to know research methods
and procedures used in the field of protein
stability and folding, which comprise biophysical
methods, biochemical methods and various
spectroscopies: fluorescence, CD, NMR, FTIR,
- The student will develop critical thinking,
- The student will develop communication skills to present research achievements,
- Cooperation, team work,
- The student will gain insight in multidisciplinary approach to solve scientific problems.

Course Specific knowledge:
- This course prepares students to work in basic research projects,
- The knowledge is important for biotechnology and food technology,
- It provides a molecular understanding of some pathological processes – related to biomedicine.

Metode poučevanja in učenja:

Learning and teaching methods:

Predavanja, konzultacije, individualno delo, laboratorijsko delo (samo v primeru mentorstva)

Lectures, consultations, individual work, laboratory work (If supervising the student)

Načini ocenjevanja:

Delež v % / Weight in %

Assesment:

Ustno izpraševanje

100 %

Oral assesment

Reference nosilca / Lecturer's references:

1.	HASANBAŠIĆ, Samra, TALER-VERČIČ, Ajda, PUIZDAR, Vida, STOKA, Veronika, TUŠEK-ŽNIDARIČ, Magda, VILFAN, Andrej, BERBIĆ, Selma, ŽEROVNIK, Eva (2019). Prolines affect the nucleation phase of amyloid fibrillation reaction; mutational analysis of human stefin B. ACS chemical neuroscience, ISSN 1948-7193, 2019, vol. 10, no. 6, str. 2730-2740, doi: 10.1021/acschemneuro.8b00621
2.	ŽEROVNIK, Eva (2021). Viroporins vs. Other Pore-Forming Proteins: What Lessons Can We Take? Front Chem. 2021 Feb 18;9:626059. doi: 10.3389/fchem.2021.626059. eCollection 2021. review
3.	Venko K, Novič M, Stoka V, Žerovnik E. (2021). Prediction of Transmembrane Regions, Cholesterol, and Ganglioside Binding Sites in Amyloid-Forming Proteins Indicate Potential for Amyloid Pore Formation. Front Mol Neurosci. 2021 Feb 10;14:619496. doi: 10.3389/fnmol.2021.619496. eCollection 2021.
4.	ŽEROVNIK, Eva (2022). Human stefin B: from its structure, folding, and aggregation to its function in health and disease. Front Mol Neurosci. 2022 Oct 21;15:1009976. doi: 10.3389/fnmol.2022.1009976. eCollection 2022. review
5.	Žganec M, Taler Verčič A, Muševič I, Škarabot M, Žerovnik E. (2023). Amyloid Fibrils of Stefin B Show Anisotropic Properties. Int J Mol Sci. 2023 Feb 13;24(4):3737. doi: 10.3390/ijms24043737.