BIOMG 1350 Fall 2024 Past Papers PDF

L24: Telomeres, Telomerase, and Aging ECB6: 210-211 (review from lecture 3) ECB6: 223-225 Learning objectives: Understand the basics of DNA replication Understand the end-replication problem Know that telomeres are heterochromatic repetitive DNA sequences Le...

L24: Telomeres, Telomerase, and Aging ECB6: 210-211 (review from lecture 3) ECB6: 223-225 Learning objectives: Understand the basics of DNA replication Understand the end-replication problem Know that telomeres are heterochromatic repetitive DNA sequences Learn that telomerase is a ribonucleoprotein that elongates chromosome ends Understand the concept of cell senescence Realize the connection between telomere attrition, Essential Cell Biology, Fifth Edition stem cell senescence, and organismal Copyright © 2019 W. W. Norton & Company  BIOMG1350 PRELIM 4: December 9th, 2024 (L19-24; S10-11) check your room/seat assignment by Saturday practice prelim will be uploaded today review sessions with TAs 1-4PM this Sat/Sun in G01 Biotech BIOMG 1350 FINAL EXAM: Saturday 12/14/2024 9:00 AM BTN100CENT, BTN100EAST Location Barton Hall. BTN100CENT, BTN100EAST We are trying to make previous prelims available for practice Review sessions with TAs 1-3PM December 12th Thursday – Biotech G01 (Racker room) December 13th - Friday – Room TBD (Warren Hall 101, tentative) Watch for instructions announcement next week It is your responsibility to read and know the rules, including academic integrity issues BIOMG 1350 MAKE-UP FINAL EXAM REQUEST: DEADLINE Wednesday Dec 4 th send request to [email protected] with a reason for wanting a make-up exam  a list of ALL your final exams with their course number, date, and time  conflicts will be scheduled between Dec 16 th - 20th, date and location TBD  Adult Stem cells Embryonic stem cells Stem Cells L23 wrap-up Reprogramming: iPS cells Applications iPS cells can be used to study and treat genetic disease Cultured ES (or iPS) cells can give rise to a three- dimensional organoid.  Organoids can also be obtained from tissue SCs Sato and Clevers (2013) Science 340: 1190 Adult hematopoietic stem cells are frequently used in clinics Find immune- Inject the cells into Use strong compatible donor and the chemotherapy or collect stem cells to bloodstream of the radiation to kill the transplant. patient; stem cells cancer cells, but this will find their way treatment also kills to the marrow and hemopoietic stem repopulate the cells. blood.  Basic Science Applications of ESCs: The Nobel Prize in Physiology/Medicine 2007 for introducing specific gene modifications in mice via embryonic stem cells Gene targeting to introduce mutations (e.g. CRISPR/Cas9) Mutant ES cells (gene KO) Breeding to transmit mutation to next generation of mice Blastocyst develops in Clump of mutant foster mother into a ES cells injected in chimeric mouse; the blastocyst ES cells contribute to all Figure 22-40 MBC6e tissues Example of gene knockout experiment: leptin knockout mice are obese * KO experiment helped show that leptin is a hormone which regulates body fat as well as the sensation of hunger, and its loss results in obesity, susceptibility to diabetes, and other complications.  Stem cells and cancer 1) Stem cells are likely the origin of many cancers long-lived ->accumulate mutations proliferative -> more prone to transformation evidence of ‘cancer stem cells’ – rare tumor cells can rebuild a tumor 2) Stem cells regulatory signals are often perturbed in cancer Quiescence signals -> inactivated Activation signals -> super-activated Differentiation signals -> inactivated or aberrant Stem cell renewal and pro-cancer pathways are linked Reya et al. (2001) Nature 414:105  BIOMG1350 Overview Macromolecule Macromolecules Developmental Biology Cellular Structures Stem Cell Biology Building Blocks & Synthesis & Processes & Embryogenesis & Homeostasis L24: The Biology of Aging  How long can we live? The oldest age to which any person on record has lived was a French woman, Madam Jeanne Calment, who was born in the small town of Arles on February 21, 1875 and died August 4, 1997 at age 122 years, 164 days What are the causes and how can we prevent aging? Longevity has: - a moderate genetic component - an environmental component An important molecular contributor to aging is the inability to fully replicate and hence maintain telomere length in tissue stem cells (along with several other causes)  Telomeres are heterochromatic regions devoid of genes and made of repetitive DNA sequences Telomeres length is genetically determined and varies from species to species, person to person, and even cell type to cell type; it declines with age. Review “Replication” & “Telomerase” from lecture 3 : ECB6 210-211  Telomerase: a ribonucleoprotein that replicates the ends of eukaryotic chromosomes RNA (TERC or TR): Used as template (in San Diego, California, USA) Nobel Prize for Medicine in 2009 protein (TERT): reverse transcriptase = synthesizes DNA from an RNA template  DNA REPLICATION: SUMMARY Please review DNA replication and telomerase from lecture 3 and the video in this lecture DNA Polymerase Synthesizes DNA Using a Parental Strand as a Template The Replication Fork has a leading and a lagging DNA strand Short Lengths of RNA Act as Primers for DNA Synthesis DNA synthesis on the lagging strand occurs in fragments (Okazaki Nucleases and ligases cooperate with primase and DNA polymeras to synthesize DNA on lagging strand The end-replication problem = incomplete replication on the lagging strand Telomeres are heterochromatic regions made of repetitive sequences Telomerase extends the chromosome ends from its RNA template  Figure 2 Telomere attrition results in permanent cell cycle arrest (i.e. cell senescence) Cell culture experiments Cells w/o telomerase reach critically short telomeres and stop their proliferation This is called the “Hayflick limit” and results in cell senescence, a form of cellular ‘aging’ Senescent cells do not die but they permanently withdraw from the cell cycle Senescence is a form of tumor- suppression (prevents cancer) Restoring telomerase activity in these cells restores their Current Biology 1998 8R178-R181DOI: (10.1016/S0960-9822(98)70105-8)  Telomere length and telomerase activity varies in different cell types of an organism High telomerase activity Tiss ue Pr iffe D Medium/low telomerase activity og re en n t it iat or e an d c d e Low/absent telomerase activity lls Shutting down telomerase & cell senescence in adult tissue are mechanisms that suppress cancer. ps://www.spandidos-publications.com/ijo/43/5/1351  Senescence of tissue stem cells may contribute to aging TERC (RNA component) Knockout Mice: Early generation : no phenotype due to mice having very long telomeres Late generations (5th): phenotypes show defects in tissue homeostasis - Infertility: increases with generation- due to germline SCs apoptosis - Diskeratosys congenita—like phenotypes -- due to limited tissue SC proliferation (a disease of poor telomere maintenance with some characteristics of premature aging) Defective closure of neural tube (NSC) Small size/atrophy of the intestine (ISC) Abnormal skin pigmentation Defective skin/nail/hair regeneration TERT (protein Bone marrowcomponent) failure Over-expression Mice: Live longer Death (but have higher incidence of cancer) Telomerase and telomere length represent only one factor contributing to organismal aging A few examples of candidate aging factors are: Epigenetic changes and spurious transcription Accumulations of mutations due to replication errors and other challenges Changes in the ECM or cellular composition of the stem cell niche Altered signals that perturb cell-cell communication Endocrine signals (young vs old blood) Circulatory factors contribute to tissue stem cell decline and organismal aging ‘Heterochronic parabiosis’ = joining blood circulation of old and Oldyoung Young mice Old Young Exposing aged mice to a more youthful systemic environment promoted stem cell activity and tissue Exposing young regeneration/activity mice to an aged systemic environment Endocrine signaling induced impaired stem cell activity and tissue decline  Nine proposed hallmarks of organismal aging Cell. 2013 June 6; 153(6): 1194–1217. doi:10.1016/j.cell.2013.05.0  Interventions that Might Extend Human Healthspan The nine hallmarks of aging are shown together with those therapeutic strategies for which there are proof of principle in mice. Cell. 2013 June 6; 153(6): 1194–121