Izučavanje geneze pogrešaka u diobi živih stanica

master's thesis

• Title (english): Studying origins of missegregations in living cells
• Author: Veronika Pisačić
• Mentor: Nenad Pavin (mentor)
• Committee member: Nenad Pavin (predsjednik povjerenstva)
• Committee member: Matko Glunčić (član povjerenstva)
• Committee member: Vedran Đerek (član povjerenstva)
• Committee member: Tomislav Bokulić (član povjerenstva)
• Committee member: Danko Radić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Physics); Zagreb
• Defense date and country: 2022-09-27, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Physics

Abstract

Mnoge tumorske stanice posjeduju neispravan broj kromosoma i jedno od gorućih pitanja je objasniti koji mehanizmi tijekom evolucije stanica dovode do pojave stanica s neispravnim brojem kromosoma, tzv. aneuploidnih stanica. Iako je aneuploidija iznimno štetna za većinu stanica te uzrokuje njihovu smrt, to nije slučaj kod tumorskih stanica. Stoga nam je od iznimne važnosti otkriti što omogućava aneuploidnim stanicama preživljavanje i toliko brzo reproduciranje u tumorima. Da bi to otkrili razvijen je matematički model koji opisuje evoluciju stanica s određenim brojem kromosoma, tj. s određenim kariotipom. No, kako je broj različitih kariotipa jako velik, uvodimo novi koncept, makrokariotip, te tražimo stacionarno rješenje rate jednadžbe. Problem se potom svodi na svojstvenu jednadžbu koju rješavamo numerički koristeći programski jezik Phyton. Detaljom analizom stanica s maksimalno dvije kopije kromosoma možemo zaključiti da iako se aneuploidne stanice 20% sporije proliferiraju, uz jednaku vjerojatnost za apoptozu kao i ostale stanice, one će u potpunosti prevladati. Također, povećanjem vjerojatnosti misegregacije jedne kopije kromosoma, prevladavaju aneuploidne stanice neovisno o tome što se proliferiraju sporije i imaju veću vjerojatnost za smrt. Osim toga, istražili smo i ponašanje sustav u kojem imamo izdvojen jedan od kromosoma, kromosom 15, te smo zaključili da će takve stanice prevladavati ili zbog njihove smanjene apoptoze ili zbog smanjene apoptoze u kombinaciji s njihovom povećanom proliferacijom.

Abstract (english)

Many tumor cells have an incorrect number of chromosomes and one of the burning issues is to explain which mechanisms during cell evolution lead to the occurrence of cells with an incorrect number of chromosomes known as aneuploid cells. Although aneuploidy is extremely harmful to most cells and causes their death, this is not the case with tumor cells. Therefore, it is extremely important for us to find out what enables aneuploid cells to survive and reproduce so quickly in tumors. To discover this, a mathematical model was developed that describes the evolution of cells with a certain number of chromosomes, i.e. with a certain karyotype. However, since the number of different karyotypes is very large, we introduce a new concept, the macrokaryotype, and look for a stationary solution of the rate equation. The problem is then reduced to a eigenvalue problem that we solve numerically using the Python. By detailed analysis of cells with a maximum of two chromosome copies, we can conclude that although aneuploid cells proliferate 20% more slowly, with the same probability of apoptosis as other cells, they will completely prevail. Also, by increasing the probability of missegregation of one chromosome copy, aneuploid cells predominate regardless of the fact that they proliferate more slowly and are more likely to die. In addition, we investigated the behavior of a system in which we have isolated one of the chromosomes, chromosome 15, and we concluded that such cells will prevail either because of their reduced apoptosis or because of reduced apoptosis in combination with their increased proliferation.

• Keywords: tumorske stanice; aneuploidija; matematički model; kariotip; makrokariotip; rate jednadžba; proliferacija stanica; apoptoza; misegregacija kromosoma
• Keywords (english): tumor cells; aneuploidy; mathematical model; karyotype; macrokaryotype; rate equation; cell proliferation; apoptosis; chromosome missegregation
• Language: croatian
• URN:NBN: urn:nbn:hr:217:436561
• Study programme: Title: Physics; specializations in: Research; Course: Research; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra fizike (magistar/magistra fizike)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-10-20 07:48:32