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Cell Biology (311) > Lecture 1- Cell Biology and Society > Flashcards

Lecture 1- Cell Biology and Society Flashcards

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1
Q

Topic 1- mRNA vaccines and COVID

Who first suggested synthetic mRNAs? and for what?

A
  • Katalin Kriko, Hungarian-born scientist at UPenn
  • Suggested as a means to address diseases

But she didn’t get grant money and was demoted

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2
Q

Topic 1- mRNA vaccines and COVID

What were the two problems with mRNA?

A
  • mRNA causes an immune reaction
  • mRNA can be degraded
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3
Q

Topic 1- mRNA vaccines and COVID

What was the solution for mRNA causing an immune reaction and being degraded?

A

changing a few of the bases, called modified mRNA

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4
Q

Topic 1- mRNA vaccines and COVID

What needed to be overcome once modified mRNA was developed?

A

How to get the naked mRNA into cells so that it could synthesize the target protein of itnerest and secrete it

(inject lipid nanoparticles)

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5
Q

Topic 1- mRNA vaccines and COVID

How did modified mRNA become a big thing? (critical application)

A
  • Bio tech companies like Pfizer/BionTech and Modera took notice, and COVID hit with a vengance
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6
Q

What was Katalin Kariko awarded a nobel prize for?

A
  • Nobel Prize in Physiology or Medicine for her work with Drew Weissman in 2023
  • for mRNA idea
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7
Q

Topic 1- mRNA vaccines and COVID

mRNA vs. trad vaccine: components

A
  • mRNA vaccine: contains mRNA
  • trad vaccine: contains microbial protein or inactive microbe
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8
Q

Topic 1- mRNA vaccines and COVID

mRNA vs trad vaccine: production

A

mRNA: faster bc mRNA molecules are easier to produce
trad vaccine: slower and more difficult to produce the right type of protein

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9
Q

Topic 1- mRNA vaccines and COVID

mRNA vs trad vaccine: process

A

mRNA: components injected into the arm and serve as instructions for the body to make microbial protein. Closely mimics a native viral infection leading to B and T cell responses

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10
Q

Topic 1- mRNA vaccines and COVID

mRNA and trad vaccine similarities

A
  • both are antigens determined for immune stimulation
  • both teach the body to protect itself against a microbe
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11
Q

Topic 2: Plants

“Fighting Cancer with a Pinch of Parsley and Dill” (seed)

A
  • extracts from parsley ad dill seeds are a new source of a precursor of GVA (an antimitotic drug now more easily synthesized)
  • GVA inhibits the growth of tumor cells by halting cells in mitosis and is not cytotoxic to normal cells
  • CellInsight Cx5 High Contenct Screening (HCS) used to visualize
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12
Q

Topic 2: Plants

What is GVA?

A

an antimitotic drug that inhibits the growth of tumor cells by halting cells in mitosis, but is not cytotoxic to normal cells

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13
Q

Topic 2: Plants

What is CellInsight CX5 High Content Screening (HCS)?

A
  • automated imaging platform that acquires high-resolution images of stained cells
  • allows researchers to evaluate the effects of various drugs on cellular functions by capturing and analyzing images of cells in large quantities (valuable for large-scale, high-throughput experiments in drug discovery)
  • Gains quantitative data
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14
Q

Topic 2: Plants

Making Photosynthesis better

A
  • photosynthesis efficiency is less than solar panels (range around 0.1%-2% effective)… but works well enough that evolution doesn’t try to improve it
  • So scientists try to improve it
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15
Q

Topic 2- Plants

1/4/2019: “Synthetic glycolate metabolism pathways stimulate crop growth and productivity in the field”

A
  • Major enzyme (RUBISCO) in photosynthesis sometimes uses oxygen rather than CO2, resulting in glycolate (which is toxic). Wasteful process called photorespiration- reduces efficiency by 50%
  • So, researchers from the USDA and U of Illinois made transgenic tobacco plants (model organisms) that process glycolate in only one cellular compartment rather than throughout the entire cell.
  • As a result, photosynthesis improved and plants grew 40% more biomass
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16
Q

Topic 2: Plants

12/9/2022: “Photosynthetic Mammalian Cells Slow Degenerative Disease”

A
  • Researchers have generated photosynthetic human cells by transplanting “nanothylakoid units (NTU)” (engineered mini chloroplasts) into them
  • When transplanted into degenerating cells in mice with osteoarthritis and illuminated, disease progression is prevented
  • Works because NTUs produce ATP and NADPH (more energy and reducing agents) that may also be important to prevent againg as well as diseases
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17
Q

Topic 2: Plants

1/14/2021: “Plant-based Biomanufacturing a Growing Trend”

A
  • Most biologics (drugs that are either made in cells through genetic engineering or harvested from native plants…come from something living) are generated in animal cells
  • But now many like Pfizer’s elelyso to treat Gaucher disease is made in plants
  • Department of Defense (DARPA) currently has a $100 M grant programto support plant biopharmaceutical technology
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18
Q

Topic 3- Transplants

Overview from “Transplants Without a Waiting List- Can Cell Biologics Help?”

A
  • UNOS- United Network for Organ Sharing
  • Demand outpaces the supply
  • But 3-D tissue engineering may alter the transplant landscape
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19
Q

Topic 3- Transplants

3/21/2024: HMS+MGH, “In a First, Genetically Edited Pig Kidney is Transplanted into Human”

A
  • Physicians transplanted a genetically engineered pig kidney that had 69 genes modified to make it less likely to cause immune rejection when transplanted into a patient (Xenotransplantation). The patient died 2 months later
  • This pioneering “compassionate case” speaks to the power of cell/molecular biology and its role in the future of organ transplants
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20
Q

Topic 3- Transplants

Do we know enough about cell and molecular biology to make an artificial organ or tissue?

A
  • Yes- it has been done
  • Tissue engineering is a sub-discipline of regenerative medicine… includes building tissues in the lab that can use adult stem cells, somatic cells, or human embryonic stem cells
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21
Q

Topic 3- Transplants

“Organoid Culture to Match Human Small Intestines”

A
  • Tissue engineered intestinal organoids developed in the Netherlands that generate paneth cells
  • Not previously inclued in intestinal organoids, Paneth cells defend the intestine from pathogens with secreted proteins called “defensins”
  • Defective or missing Paneth cells occurs in diseases such as inflammatory bowel disease
  • So, this model better represents a tissue construct that can be used for testing new drugs for intestinal diseases
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22
Q

Topic 3- Transplants

Fully Functioning Artificial Human Heart Muscle Organoids

A
  • Several research teams are developing cardiac organoids
  • They could be used in the future as “band aids” subsequent to a cardiac event such as an infarct
  • Alternatively, they could be used for drug discovery to identify drugs that can treat arrhythmia
  • Tracy Hookway’s lab (Natalie Pachter) in BU’s BME is developing a cardiac fibrosis model that could in the future help screen for drugs that can treat cardiac fibrosis
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23
Q

Topic 3- Transplants

But can we make multi-chambered heart organoids? “Multi-Chambered Heart Organoids Allow Study of Organ Development and Defects”

A
  • Scientists in Austria have developed a multi-chamber organoid that mirrors the heart’s intricate structure
  • Applications: not for transplant but can be used in drug development and toxicology studies as well as heart development and defects
  • Importance: cardiovascular disease is the leading cause of death worldwide
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24
Q

Topic 3- Transplants

“Organoids” such as a brain organoid can be generated from a variety of stem cells. But, can we transplant animal neurons into human brains to regenerate damaged circuits (may be possible in future)? “In a First, Neurons from Rat Stem Cells Regnerate Brain Circuits in Mice”

A
  • Rat olfactory (smell) neural circuits were restored by mice stem cells that formed circuits in rats that lacked the circuit
  • This suggests that this restorative application may be possible in aging or diseased humans using cells generated from humans or animals
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25
Q

Topic 3- Transplants

What is done to kidneys as the starting point to build a tissue engineered kidney?

A
  • A donor kidney can be “decellularized” and then seeded with new stem cells as the starting point to build a tissue engineered kidney
  • preserves the extracellular matrix as a structural scaffold
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26
Q

Topic 4-Nanomedicine

“Time Release Microparticles Could Deliver ‘Self-Boosting’ Vaccines”

A
  • Most vaccines require multiple shots/boosters to be effective
  • MIT bioengineers have created microparticles containing vaccine that could be implanted under the skin and “time-tuned” to release several “shots” in a process called “self-boosting vaccines”
  • They are given only once and designed to boost spontaneously at specified times
  • They resorb over time like degradable sutures
  • Advantage: childhood vaccines in regions where ppl don’t have frequent access to medical care
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27
Q

Topic 4-Nanomedicine

“Tine Robots Detect and Treat Cancer by Traveling Deep into the Lungs”

A
  • Tiny robot which travels deep into the lungs to treat cancer has been developed
  • Ultrasoft tentacle which is 2 mm in diameter is controlled by magnets
  • Can penetrate inaccessible lung cancer tissue deeper than conventional technology, resulting in less damage releasin chemotherapy agents
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28
Q

Topic 4-Nanomedicine

“Chinese use Nanomedical editing techniques (CRISPR-Cas9) on pre-implantation Human Embryos”

A
  • CRISPR-Cas 9 discovered in 2008 was intended for lab use
  • But a team using human embryos attempted to modify the gene reponsible for B-thalassaemia, a potentially fatal blood disorder using CRISPR
  • Concerns now the Eugenics may happen in the future
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29
Q

Topic 4-Nanomedicine

“Chinese scientist claims birth of world’s first CRISPR babes, amid denial from hospital and international outcry”

A
  • He Jiankui, he was fined and put in jail
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30
Q

Topic 4-Nanomedicine

“GEN-CRISPR Babies Researcher He Jiankui Sentenced to Three Years in Prison”

A
  • 13 months after touching off an itnernational firestorm w his research that led to the birth of three germline-edited babies, He Jiankui was sentenced by Chinese authorites to 3 years in prison and a fine of 3M yuan ($430,000)
  • J. Craig Venter applauded Chinese government for this
  • Now can do experiments that are unethical. So, gov regulation is required in some cases like this one
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31
Q

Topic 4-Nanomedicine

“FDA Approves Casgevy, the First CRISPR Therapy, for Sickle Cell Disease”

A
  • US FDA approved Casgevy- the first CRISPR-based gene editing therapy for sickle cell disease
  • SCD was named by Linus Pauling the first “molecular disease” discovered and SCD children are born every 2 mins w 100,000 affected in the US
  • Developed by Boston’s Vertex Pharmaceuticals- Patient stem cells are harvested and CRISPR is used to turn on fetal hemoglobin
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32
Q

Topic 5: Synthetic Biology

What is synthetic biology?

A
  • Synthetic biology is the engineering discipline that encompasses the synthesis or creation of complex, biologically based/inspired systems which display functions that do not exist in nature using cell.molecule biology tools and techniques
  • Ex. Engineered antibodies called bispecific trifunctional antibodies
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33
Q

Topic 5- Synthetic Biology

What are Bispecific, trifunctional antibodies?

A
  • engineered antibodies used to treat cancer
  • bring tumor cells together with killer T cells and Accessory cells (macrophages, natural killer cells, etc) so that the T cells can kill the cancer cells
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34
Q

Topic 5: Synthetic Biology

“Mechanisms in Aging Process Illuminated by Light Powered Mitochondria”

A
  • Recent report of developing “optogenetically responsive mitochondria” to generate more ATP from mitochondria
  • Cells were generated in C.elegans (translucent roundworm) that have a light sensitive proton pump in the mitochondria that when illuminated is similar to recharging rechargeable batteries. When the light is on more protons are pumped by the optogenetically designed proton pump and more ATP is generated
  • So what happens to these C. elegans? They are healthier and their lifespan is extended. The researchers compare this to a “solar panel system” for mitochondria
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35
Q

Topic 5: Synthetic Biology

Who is J. Chraig Vener and why did he make history in cell and molecular biology?

A
  • First self-relicating synthetic bacteria cell
  • Researchers at the J. Craig Venter Institute (non profit genomic research org) published results describing the successful cnotruction of the first self-replicating synthetic bacteria cell.
  • Team synthesized the 1.08 million bse pair chromosome of a modified Mycoplasma mycoides (bug that infects goats) and is the proff of principle that genomes can be designed in the computer, chmeically made in the lab, and transplanted into a recipient cell to produce a new self-replicating cell controlled only by the synthetic genome.
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36
Q

Topic 5: Synthetic Biology

What was the process for making the first self-replicating synthetic bacterial cell?

A
  1. Entire DNA of Mycoplasma mycoides
  2. Researchers buy fragments of DNA from a mail order catalogue. Each of the the four bottles of chemicals contains a section of the code.
  3. The fradments are putinto yeast, which “stitches” them together, gradually building a synthetic copy of the original DNA
  4. The artifical DNA is put into a recipient bacterium, which then grows and divides creating two daughter cells (one with the artifical DNA and one with the natural)
  5. Antibiotics in the petri dish kill the bacteria with the natural DNA, leaving the one with the synthetic DNA to multiply
  6. Within just a few hours, all traces of the recipient bug are wiped out and bugs with artificial DNA thrive.
  7. Possible uses are bugs capable of producing clean fuels and sucking CO2 out the atmosphere, mopping up oil spills, or generating drugs
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37
Q

Topic 6: Lab (Organs) on a Chip

What are labs/organs on a chip?

A
  • New microfluidic devices called “labs/organs on a chip” promise to improve and change the field of disease diagnostics such as cancercell detection
  • Evolved from advances in tissue engineering
  • Now being used for drug toxicity testing call “in vitro toxicology” among many other things
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38
Q

Topic 6: Lab (Organs) on a Chip

Wyss Institute-Harvard University: “Fluidically linked BBB and Brain Organ Chips offer new method for studying the effects of drugs and disease on the brain and its blood vessels”

A
  • Goal is to make 10 different “lab on a chip” human mimetic “organs” and hook them up together so that they can work for 4 weeks
  • They reported a BBB 3 chip system that can be used to study BBB functions
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39
Q

Topic 6: Lab (Organs) on a Chip

“Heart Attacks Mimicked on a Chip”

A
  • Scientists at the University of Southern California have developed a heart attack on a chip
  • One big problem with heart attacks is to better understand what happens in the heart atthe no oxygen/with oxygen border or interface in the cardiac tissue
  • This 2 part chip device can model this interface. In contrast, this can’t be studied in real time in animal models
  • Will be useful to identify new drugs to treat heart attack after the infarct (dead tissue from failure of blood supply) and to better understand how the cardiomyocytes (cells of cardiac muscle) respond to this oxygen/no oxygen border
40
Q

Topic 7: Inherited Diseases

What is going on w genetic testing?

A
  • Research by cell and molecular biologists have resulted in genetic tests that can predict disease states and health issues.
  • There are hundreds of different genetic tests with the number of tests sold doubling every year for the past year.
  • But not all are FDA approved and many are direct to consumer which can be problematic given that the public is now interpreting the results without physician guidance and counseling
41
Q

Topic 7: Inherited Diseases

What happened with Dr. Zhang?

A
  • New Hope Fertility center Dr. who did IVF technique using three parents
  • Uses nuclear transfer and three parents to prevent mitochondrial diseases in newborns
  • FDA reprimanded Dr. Zhang
42
Q

Topic 7: Inherited Diseases

How does the three parent IVF technique work?

A
  1. Healthy nuclear DNA removed from patient’s egg cell, leaving behind faulty mitochondrial DNA
  2. Patient’s nuclear DNA transplanted into donor egg w helathy mitochondrial DNA
  3. Reconstructed egg cell fertilized with sperm in the lab and implanted into the patient.

legal in UK but not the US

43
Q

Topic 8- Biomarkers

What forms do biomarkers come in?

A

molecular marker (ex. protein), circulating tumor cells (CTCs), cell free DNA (cfDNA), exosomes (extracellular vesicles), or microvesicles that indicate the status of a possible or pre-existing disease state sampled via “liquid biopsy” (blood, urine, or CSF)

44
Q

Topic 8- Biomarkers

Liquid biopsies vs tissue biopsies

A
  • Blood biopsy analysis takes a few days, not up to 6 weeks- much better for patient
  • Blood contains cfDNA from dead and recycled cancer cells- a very promising field
  • Availability of biopsy services is more limiting for tissues than blood (any clinic can draw blood)
45
Q

What is the difference between CTCs and cf-DNA?

A
  • CTCs are intact cancer cells that have detached from the primary tumor and circulate in the bloodstream, contribute to metastasis
  • cfDNA is fragments of DNA released into the bloodstream (usually from dead or dying cells)
  • CTCs more useful for studying metastasis and cell behavior, where cfDNA is used for genetic profiling of tumors and tracking mutations over time
46
Q

Topic 8- Biomarkers

What is the Galleri test?

A
  • Analyzes cfDNA to detect 50+ types of cancer w a 99.5% accuracy rate
  • Qualitative, next-generation sequencing-based, in vitro diagnostic test intended for the detection of DNA methylation patterns using cfDNA isolated from human peripheral whole blood
  • Developed by Californian healthcare company Grail, and was piloted w 165,000 patients in a “world-first deal”… backed by Bezos and Gates
  • Works by analyzing cfDNA shed from tumor cells. $1250/test w 2 week turnaround. Must be done via health provider
47
Q

Topic 8- Biomarkers

What is DNA methylation?

A
  • Natural process used by cells to regulate gene expression
  • Certain DNA methylation patterns can serve as a signal of cancer and provide information about the origin of the cancer signal
48
Q

Topic 8- Biomarkers

“Elizabeth Holmes foudn guilty on four out of 11 federal charges”

A
  • Elizabeth Holmes was former CEO and founder of Theranos, and was found guilty of defrauding investors
  • Holmes began courting the press that Theranos had inventedtech that could accurately and reliably test for a range of conditions using just a few drops of blood taken from a finger prick- but was all fraudulent
  • She started Theranos at 19 after dropping out of Stanford and got outside parties to invest $950M. But whistleblower said data was fraudulent
  • Sentenced to 11 years in prison
49
Q

Topic 8- Biomarkers

Cynvenio Biosystems

A
  • Makes a liquid biopsy device for the immunomagnetic (antibodies) and microfluidic capture of CTCs
  • Uses antibodies that bind to the proteins on CTCs’ surface. The antibodies are attached to magnetic particles, so once the anibodies bind to the CTCs the particles are separated from the rest of the blood using a magnetic field
50
Q

Topic 8- Biomarkers

“Microfluidic Extraction of CTCs from liquid biopsies”/ Vortex

A
  • Relies on unique physical characteristics of CTCs to capture them in microfluidic vortex, like eddies in a river
  • WBCs and RBCs move down the river faster, leaving CTCs behind.
  • They are collected and counted- no antibodies used
  • This tech is nature inspired bc the vortex is naturally occuring in rivers
51
Q

Topic 8- Biomarkers

“Microfluidic Flows Enter Medical Mainstream”

A
  • CTC extraceluular vesicles exosomes might be a better biomarker for someone’s cancer burden (higher in abundance and carry genetic/molecular info)
  • Microfluidic devides that can capture CTC exosomes are being developed and tested
52
Q

Topic 8- Biomarkers

“Nanotechnology for Isolating Disease Biomarkers from exosomes in tears”

A
  • A nanomembrane system that harvests exosomes from tears named iTEARS has been developed
  • Collecting exosomes from tears is less invasive than from blood and may predict diseases, etc and only takes 5 minutes
  • Can detect different types of dry eye syndrome, and others. Not in the clinic yet
53
Q

Topic 9- New developments and challenges in cancer therapies

What are cancer stem cells?

A
  • Very low in number and don’t respond to standard cancer treatments. Can be quiescent (dormant) for years
54
Q

Topic 9- New developments and challenges in cancer therapies

Tumor Microenvironment

A
  • Through extracellular signaling tumor microenvironment can keep cancer cells in non proliferating form or can trigger proliferation and metastasis
55
Q

Topic 9- New developments and challenges in cancer therapies

Conjugated and Bispecific Antibodies

A
  • Can kill cancer cells in different ways
  • Conjugated antibody: antibody attached to a substrate
  • Bispecific antibody: designed to bind to 2 different antigens at the same time
56
Q

Topic 9- New developments and challenges in cancer therapies

Genetically Modified T Cells

A
  • When injected into chronic lymphocytic leukemia patients, hones in on the cancerous B cells inside the bone marrow which kills them
  • Now being tested at many venues
57
Q

Topic 9- New developments and challenges in cancer therapies

Immunomodulators

A
  • Cancer cells have a “don’t kill me” signal that prevents our immune system from killing tumor cells.
  • New drugs now block this don’t kill me signal
58
Q

Topic 9- New developments and challenges in cancer therapies

“How Migrant Cancer Cells Sleep for Years before Reawakening”

A
  • Cells that leave an original or “primary” tumor can remain in a non-cancerous, dormant state for years before awakening to generate tumors at other locations in the body- a stage in cancer progression called ‘metastatic cancer’
  • The authors show scattered cancer cells remain in a dormant state preventing the recurrence of metastatic tumors if the environment of these cells is enriched with Type 3 collagen- an extracellular matrix protein
  • When the scientists increased the amount of type 3 collagen around cancer cells that had left a tumor, cancer progression stalled and the disseminated tumor cells maintained a dormant state. But when the tumor cell stops making type 3 collagen it converts from dormant to metastatic
59
Q

Topic 10- Biotechnology

What is biotechnology?

A
  • Diverse set of disciplines designed to develop new medical devices, drugs, biomarkers, engineered cells, etc. for the purpose of improving human health and welfare
  • CPSI Biotech in Owego, NY… recently developed a new clinical cryosurgical device that will be in the clinic soon
  • Works on super freezing target tumors such as pancreas
60
Q

Topic 11- Personalized Medicine

What is personalized medicine?

A

Treating patients baased on their own unique genomic/proteomic profiles

61
Q

Topic 11- Personalized Medicine

$1000 genome

A

Whole genome sequencing can now be done for less than $1000 as of 2012/2013

62
Q

Topic 11- Personalized Medicine

23 and me

A
  • Capitalized on genome sequencing market and developed an ancestry and health predisposition report currently as of 2024 that costs $139
  • But FDA told them to stop selling their kits bc they went from ancestry to include diagnostics, health reports, etc.
  • In 2023 23 and Me complied w the FDA and now offers: Ancestry reports, trait reports, health predisposition reports, carrier status reports, wellness reports, and pharmacogenetics reports
63
Q

Topic 11- Personalized Medicine

Genesight

A
  • Company uses DNA samples to predit how the efficacy of select medicines used for depression can be influenced by your own DNA- very important in COVID age
  • Doc collects cheek swab, it is sequenced at Genesight, then results are sent to the Dr.
  • Known pharmokinetic genes that process medications are analyzed for variations that can alter the medicine efficacy and breakdown products in each patient
64
Q

Topic 11- Personalized Medicine

Personalized Medicine is Now in the Clinic

A
  • Myriad Genetics distributes a number of kits for predicting breast and prostate cancer including Polaris for prostate cancer- ran into problems w US Supreme Court
  • GenomicHealth now distributes OncotypeDX that is a genetic test used by prostate surgeons that can predict the aggressive level of individuals with prostate cancer. Helps patient determine if “watchful waiting” or “resection” would be the best treatment
65
Q

Topic 11- Personalized Medicine

Personalized Medicine Requires Protection to Human Subjects- Informed Consent

A
  • Henrietta Lacks and HeLa cells- 1951
  • GINA (Genetic Information Nondiscrimination Act). Enacted after Venter sequenced the human genome for the first time in year 2000 but before the $1000 genome was available. States that your genetic information can’t be used as a criterion for employment or medical insurance
  • Harvard’s personal Genome Project- collecting genomes for a public data base (As of 2024 more than 5,000 participants)
66
Q

Topic 12- Orphan/Rare Diseases

Spinal Muscle Atrophy

A
  • Less than 10,000 annual SMA cases so considered an orphan disease (<200,000 cases= orphan disease and grants special patient privileges)
  • SMA is leading genetic cause of death in infants and can affect an entire family (1 in 6000 babies born worldwide each year)
  • Caused by deleted and defective genes whose normal protein products are required for proper muscle-nerve connections
  • Biogen’s “Spinraza” costs 805,000/year and is an antisense oligonucleuotide that blocks the function of the defective gene through blocking protein synthesis
  • Novartis developed “Zolgensma” to treat SMA which is a $2M gene therapy product that introduces the good gene into the body via gene therapy… but two patients died of liver failure due to it
67
Q

Topic 12- Orphan/rare diseases

Fibrodysplasia Ossificans progressive

A

knowing the genetic basis doesn’t mean the cure follows immediately thereafter

68
Q

Topic 13- Religion/Bioethics

Human Embryonic Stem Cells

A
  • Human embryonic stem cells (hESCs) are derived from human embryos (blastocysts) are now in stem cell therapy clinical trials- requires the destruction of human embryos.
  • Dickey-Wicker amendment bans the use of federal research funding that uses or destroys human embryos. But the US allows these hESCs to be used in clinical trials in the US
69
Q

Topic 13- Religion/Bioethics

“Human Extra-Embryoid Model Opens New Window into Development”

A
  • Human embryos can now be made in the lab “Extra/synthetic embryo” as of 2023
  • They behave like real, natural human embryos in culture but made from stem cells
  • Most countries allow studying human embryos up to 14 days in culture but laws prevent extending this limit. But synthetic human embryos are currently exempt from this rule, so they can be used to better understand human embryonic development
  • These synthetic embryos can be implanted and result in a pregnancy in monkeys
70
Q

Topic 13- Religion/Bioethics

“Sibling Clones of Dolly the Sheep Grow to Healthy Old Age”

A
  • Dolly born at Edinburgh University in 1996- 28 yrs ago
  • Dolly was euthanized at 6 from lung disease and advanced arthritis
  • But, other clones from the same cell line are fine
  • No federal laws against human cloning but some states (like NYS) have lasws forbidding it
  • Using discarded human embryos for stem cell therapy is legal in US and in clinical trials worldwide (therapeutic cloning)
71
Q

Topic 13- Religion/Bioethics

“Rhesus Monkey Cloned via Somatic Cell Nuclear Transfer”

A
  • Cloned rhesus monkey survived for over two years now
  • Scientific rational is bcidentical NHP (nonhuman primates) are better for drug testing due to lack of genetic variability
72
Q

Topic 14- Government/Major Research Funding Sources

Who sets the priorities for research funding?

A

The president

73
Q

Topic 15- Aging

Is cell and molecular biology at a point where we can understand and stop/reverse aging?

A
  • Maybe- many factors involved, one of which may be sirtuin (longevity) genes. Overexpression increases max lifespan of fruit flies to round worms by up to 50%
  • Stem cell theory of aging (clinical trials-Longeveron)- young folks sourced stem cells are better and more plentiful
  • But other factors (mitochondria age/health, epigenetics) are probably involved as well
74
Q

Topic 15- Aging

“SIRT 6 Overexpression Extends Lifespan in Mice”

A
  • Transgenic mice that overexpress SIRT 6 results in a reduction in fraility and an increase in lifespan by 30% compared to non-transgenic mice
  • Could be because the transgenic mice are better at generating energy from stored molecules like fatty acids
  • Also, the transgenic mice exhibit fewe age-dependent cancers and blood disorders
  • Resveratrol stimulates human sirtuin genes but not practical as a drug
75
Q

Topic 15- Aging

Teloyears

A
  • Company dedicated to reading telomeres and comparing cellular age to chronological
  • From website:
  • Cellular aging is why people look and feel older/younger than their age
  • Cellular age affected by lifestyle/health habits- TeloYears uses technology to look deep inside cells to read cellular age
  • Then the info is used to develop a personalized gameplan based on cellular info found in DNA
  • Bc length of telomeres associated w how long you’ll live and how healthy you’ll be along the way
76
Q

Topic 15- Aging

Longeveron- Cell Therapy from Young Healthy Donors

A
  • Longeveron is a life sciences company developing biological solutions for aging/aging-associated diseases through the testing of allogenic human Mesenchymal Stem Cells (MSCs) that are derived from the bone marrow of young, healthy donors. Longeveron-grown Mesenchymal stem cells (LMSCs) product manufacutred in Miami
  • Currently no FDA-approved allogeneic mesenchymal stem cell treatments in the US. LMSCs in phase 1+2 of clinical trials. Hopes to be the first to offer stem cells as a safe, effective, FDA-approved treatment for some of the most chronic/life-threatening conditions (Aging fraility, alzheimers, and metabolic syndrome)
  • Announced initiation of phase 2a clinical trials of lomecel-B for alzheimer’s treatment
77
Q

Topic 15- Aging

“US Special Operations Command to Test Anti-Aging Pill”

A
  • US Special Operations Command (military) will conduct clinical trials of a pill designed to block/reduce many degenerative effects of aging
  • Is a NAD+ enhancer (may work like SIRTUINs) developed by MetroBiotech in MA, generates more ATP in mitochondria
  • “MIB-626 may also be useful to treat amyotrophic lateral sclerosis (ALS)”
78
Q

Topic 15- Aging

“Chemically Induced reprogramming to reverse cellular aging”

A
  • David Sinclair at HMS has shown that aging can be accelerated/reversed
  • Aging is driven by epigenetic changes to the genome due to age dependent double-stranded DNA breaks (epigenetics is the non base change in DNA function such as DNA methylation ad histone phosphorylation)
  • This loss of epigenetic info accelerates the hallmarks of aging
  • These changes are somewhat reversible by epigenetic reprogramming. By manipulating the epigenome, cell aging can be driven forward and backwards and can be done with select chemical cocktails
79
Q

Topic 16- Bioterrorism

What is botox and what does itdo?

A
  • Botulinum toxin
  • Blocks the release of acetylcholine
80
Q

Topic 16- Bioterrorism

Alynylam Pharmaceuticals

A
  • Now in RNAi (RNA interference) clinical trials but sued by Brenda Bass U of Utah (she lost)
  • Patisiran FDA approved in 2018 to treat a rare neurological disorder- $450k/year
81
Q

Topic 16- Bioterrorism

Macular degeneration

A

clinical trials with RNAi was the first medical application… as of 2024 100s of clinical trials underway/completed using RNAi

might be useful for huntington’s

82
Q

Topic 16- Bioterrorism

Can RNAi be used in a combo cocktail to more effectively treat cancer?

A
  • P-Glycoprotein and MDR1 (Multi-Drug Resistant Protein) are 2 cell membrane proteins that can pump toxic compounds that include cancer drugs out of cells
  • Cancer cells have very robust p-glycoproteins but siRNA directed against p-glycoprotein might be a means to block p-glycoprotein
83
Q

Topic 16- Bioterrorism

Ricin

A
  • toxic protein that comes from castor bean
  • Might be able to treat cancer as a conjugated antibody
84
Q

Topic 17- Stem cells/regenerative medicine

What is tissue engineering?

A

lab grown tissues that can be used to treat diseases, drug discovery, in vitro toxicology (ex. organs on a chip)

85
Q

Topic 17- Stem cells/regenerative medicine

What is stem cell therapy?

A

Use of stem cells from different sources to treat diseases

86
Q

Topic 17- Stem cells/regenerative medicine

What is gene therapy?

A

using gene and single base transfection technologies to cure diseases

87
Q

Topic 17- Stem cells/regenerative medicine

What are the 4 categories of stem cells?

A
  • adult stem cells
  • fetal stem cells
  • embryonic stem cells
  • induced pluripotent stem cells
88
Q

Topic 17- Stem cells/regenerative medicine

Adult stem cells

A

most popular for medical applications are adipose (fat) derived mesenchymal stem cells (adMSCs) now in more than 1000 stem cell therapy trials worldwide

89
Q

Topic 17- Stem cells/regenerative medicine

Fetal stem cells

A

amniotic, umbilical cord, placental

90
Q

Topic 17- Stem cells/regenerative medicine

Embryonic Stem cells

A
  • hESCs (human embryonic stem cells)
  • now in clinical trials since 2010
91
Q

Topic 17- Stem cells/regenerative medicine

Induced pluripotent stem cells

A
  • Cells reprogrammed from adult stem cells to behave like embryonic stem cells
92
Q

Topic 17- Stem cells/regenerative medicine

“Missouri state lawmaker charged w seleling fake stem cell treatments and claiming they are a cure for Covid 19”

A
  • Prosecutors in Missouri claimed Patricial Ashton Derges who operates “Ozark Valley Medical Clinic” locations sold falsely advertised stem cell treatment for Covid-19 that was “safe and natural”
93
Q

Topic 17- Stem cells/regenerative medicine

hESCs

A
  • easy to procure (obtain)
  • More pluripotent (greater ability to differentiate to virtually any type of cell)
  • ethical issues are a concern
  • not autologous match (self to self)
94
Q

Topic 17- Stem cells/regenerative medicine

Adult stem cells

A
  • not as easy to procure as hESC
  • Many sources (fat, hair, teeth)
  • can be autologous match
  • probably less pluripotent
  • fewer ethical issues
95
Q

Topic 17- Stem cells/regenerative medicine

Stem cells for heart attack

A
  • Scientists have taken adult stem cells from patients w chronic heart failure and injected them into their hearts, restoring lost function
    1. Srtem cells filtered from bone marrow removed from a patient’s hip, 2. cells injected into heart damage, 3. cells embed themselves and produce proteins that may signal the growth of new blood vessels and heart muscle
96
Q

Topic 17- Stem cells/regenerative medicine

Transportation problem

A

bioheart and biolife team together for first international clinical trials

Cell Biology (311) (8 decks)

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