Personal Statement Flashcards
Define symbiosis
any type of a close and long-term biological interaction between two different biological organisms, be it mutualistic, commensalistic, or parasitic.
Describe the three types of symbiosis
1) mutualism - both species benefit from the relationship
2) commensalism - one species benefits from the relationship whilst the other is neither harmed nor benefitted
3) parasitism - one species benefits whilst the other is harmed
How did symbiosis evolve?
- interaction led to evolution
- predation
- endosymbiotic theory
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Why do you think symbiosis cannot occur between the same species/ has occurred between different species?
- maintains species and diversity
- cat licking vs oxpecker and rhinocerous
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What was the most interesting concept from ‘This is Your Brain on Parasites’?
Crickets:
Hairworms produce phototaxis alterations (changes in the
responses to light stimuli) could be a part
of the wider strategy for the completion of their life
cycle
The mechanisms used by hairworms to increase the encounter
rate withwater remaina poorly understood a
- worm tampers with visuals
- releases similar chemicals to communicate with cricket
- cricket dies, worm spills out into pool (exit into aquatic enevironment favourable for reproduction), worms mate in water, females lay eggs, eggs turn to larvae, larvae bump into mosquito larvae and hide in them as cysts, mosquito larvae turn to mosquitos carrying the parasite, cricket eats mosquito, dormant cyst now inside cricket grows to a worm again, worm makes cricket go to large expanse of water, cricket drowns and dies.
- worm produces raft of neurochemicals similar to the cricket’s
- cricket attracted to light (water reflects light) (induce a positive photoaxis response)
- blind infected crickets were not attracted to light
-parasite-induced change in host phototaxis is reversible, that
is, once the nematomorph parasite is released, crickets are no
longer attracted to light.
possible mechanism:
- in the central nervous system of manipulated N.
sylvestris (wood cricket) differential expression of proteins (from the BIR; 2 family) was involved in the inhibition of apoptosis - suggests disturbance of a cellular
process could lead to a modified neural circuitry
enhanced walking
How do they know the crickets aren’t just thirsty?
- uninfected water deprived crickets did not show any positive photoaxis (they still didn’t go to the water reflecting light)
phototactic behaviour - moving towards or away from light (cyanobacteria)
How do we know the parasite causes photophilic behaviour and the photophilic behavour doesn’t cause the parasite?
- because the behaviour isn’t maintained after the parasite exits the cricket in the ater
Would be interesting to determine if polarized light, particular wavelengths, or shapes can induce the observed phototactic response or if direction of light alone is responsible for the water-seeking behavior observed for manipulated crickets.
Define parasitic manipulation
the alteration by the parasite of a host phenotypic trait in a way that enhances the parasite’s probability of transmission and survival
What is interesting about parasitic manipulation from an evolutionary perspective?
In an evolutionary context, changes in host behaviour upon parasite infection are examples of an extended phenotype, a concept introduced by Dawkins (1982). He stated that the observed host phenotype is a consequence of a parasite’s gene being expressed.
Explain how T. Gondii alters the neural activity in the amygdala of rats?
T. Gondii resides in faeces which is then digested by rats. It causes behavoural changes within the rat causing it to no longer fear cats. The rats are eaten by cats and the parasite is transferred to the intestine of the cat - a favourable place for reproduction, ( from here stable oocysts are excreted into the faeces) and the cycle is repeated.
T. Gondii blocks an innate aversion of rats for cat urine, instead producing an attraction to their pheromones, increasing the likelihood of the cat predating on the rat
Neural circuits implicated in innate fear, anxiety and learned fear all overlap which suggests T.Gondii may disrupt all of these non specifically
Sapolsky studied the rats and found T. gondii migrates to the brain, forming cysts within the amygdala, a part of the brain associated with the control of fear.
What is the behavioural manipulation hypothesis?
How does Sapolsky’s experiment provide evidence for it?
a parasite will specifically manipulate a hosts behaviour essential for enhancing its own transmission
life
Innate fear of cat pheromones share similar neurobiological substrates to with pheromones of learnt fear and anxiety like behaviours and yet infection of T.Gondii still only blocks aversion of predator odours (innate fear) and doesn’t compromise learned fear or anxiety (hence parasite is affecting only the part of the behavioural response that is important for its transmission + completing its lifecycle)
What did Sapolsky investigate and what did he find in his experiment with T.Gondii?
He investigated the distribution of the parasite in the nervous system and the specificity of T.Gondii on the behaviours affected
He found that in infected brains parasite cysts were randomly distributed over the entire brain but cyst density was particularly high in amygdala structures
He found the effect of T.Gondii on behaviour is remarkably specific; infection didn’t decrease learned fear or anxiety like behaviour but it did decrease innate fear even though all of these behaviours are closely related. The infected mammals even still retain an innate aversion to dog urine (because this mammalian predator is not important for the sexual life cycle of the predator)
How did Sapolsky know that the innate aversion of cats is not just a generic side effect of sickness? (I.e. not as aware)
Because the response of an infected animal to a non predator (rabbit) urine odour remained unchanged and they still had an innate aversion
What do mathematical models of a prey-predator-parasite system demonstrate?
A small selective increase in susceptibility of a predator to the infected prey population is sufficient to cause a significant increase in parasitic load within the predator population
(Ie. If infected prey becomes more susceptible to the predator so like the rat running to the cat then this increases parasitic load in the predator)
Describe the mechanisms of the behavioural effects of T.Gondii on the rat
T.gondii subtle tropism for the amygdala to interrupt specific brain wiring (exact mechanism still unknown)
-internalisation of olfactory receptors important for cat odor protection
Rat preservation chemical
Carosafe
6 anatomical regions of rat
CCPTAP
Cranial region - head Cervical region - neck Pectoral region - front legs attached Thoracic region - chest area Abdomen - belly Pelvic region - back legs attached
Describe what you saw during the rat dissection
Peeled the skin back from the incision point and saw the muscular and skeletal system
Latissimus dorsi muscle - retracting the arm - triangular & covers lower back
Gastrocnemius - leg muscle
Lymph glands - dark, circular, pressed against the jaw muscles
Nicitating membrane
Describe something particularly interesting from the rat dissection
Nicitating membrane
- transparent third eyelid drawn across eye for protection and to maintain moisture
human plica semilunaris (remenants of human nicitating membrane)
secretes immunoglobulins to act as an immunological barrier
- plica semilunaris is a fold of the conjunctiva in the inner corner of the human eye - Vestigial feature
Reason for loss of function: unclear but changes in habitat/eye physiology may have rendered the tissue unecessary
Did you manage to locate the encysted parasite?
No the skull was too hard to break through
thinking about skeletal structure later on - found out collapsible skeleton - ribs hinged to spine to fold down when fitting through small spaces (pressure at front causes ribs to give way and effortlessly collapse)
What is something else that fascinated you in ‘I Contain Multitudes’?
- triple symbiotic relationship between citrus mealybug that has mealybug bacteriocyte with tremblaya in it that has moranella inside it. (All three symbionts necessary for mealybug survival, trem and mor are bacteria)
Complimentary genomes - 9 enzymes required to make amino acid phenylalanine - tremblaya builds 1,2,5,6,7,8. Moranelle builds 3,4,5. Mealybug builds 9
Bizarre thing: tremblaya genome missing class of supposedly oldest genes in existence. There should be 20, some symbionts have fewer but tremblaya has none. It survives because the other two symbionts compensate for the vanished genes.
22 bacterial genes integrated into mealybug DNA but these were NOT from either tremblaya or moranella. They came from three other lineages of bacteria living in mealybug ancestors that transferred their genes into the mealybug genome. (Mealybug genome contains genes form bacteria not presently living in symbiosis with it)
Uses genes from former symbionts.
How do you think the triple symbiotic relationship evolved?
- similar to the endosymbiotic theory
- moranella and tremblaya survived endocytosis by a citrus mealybug
- as symbiont genomes were transferred to host genome the host became increasingly dependent on symbiont mechanisms, in turn reducing the original host genome
- lost genes because didn’t need them
- but doesn’t fit with idea of Junk DNA - would have thought extra genes = protection ?
- BUT: less DNA to pack has been linked to faster nutrient transport and faster cell signalling
What is the endosymbiotic theory?
Lynn Margulis - late 1900s
Theory that some of the eukaryotic cell organelles originated from prokaryotic microbes
Mitochondria and chloroplasts may have survived endocytosis by a larger cell, lived in symbiosis with it as mitochondria provided energy and chloroplasts nutrients - prokaryotic cells (mitochondria and chloroplasts) receive protection and stable environment in return = Eukaryotic cell forms
Mitochondria evolved from endosymbiotic proteobacteria (prokaryote microbe that was engulfed)
Chloroplasts evolves from endosymbiotic Cyanobacteria (prokaryote microbe that was engulfed)
Mitochondria and chloroplasts are the same size as prokaryotic cells, divide by binary fission and have circular not linear DNA
How do genes become integrated into a host genome?
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Did anyone raise any interesting questions when you presented about T.Gondii?
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Explain the symbiotic relationship between the Hawaiian bobtail squid and bioluminescent V. Fischeri
Bobtail squid light organ full of luminous V.fischeri. Bacteria light matches moonlight shining down from above and cancels out the squid’s shadow.
Squid gains camouflage, bacteria gain hospitable environment
McFall Ngai & Ned Ruby: labelled V.Fischeri cells with glowing proteins and tracked them as they journeyed you the light organ (watched symbiosis in action)
How do V.Fischeri enter the Hawaiian bobtail squid?
XXXadd more scientific detail
- Surface of light organ covered in cilia and mucus
- creates current that draws in particles of bacterial size but no larger
- microbes collect in mucus with V.Fischeri among them
- when 5 cells make contact with the squid it causes genes within the squid to turn on, these release antimicrobial chemicals that create an inhospitable environment for the other bacteria but leave V.Fischeri unharmed
- other genes code for enzymes that break down mucus releasing chemicals that attract V.Fischeri
- V.Fischeri dominates mucous layer
- nester squid through bottleneck and reach crypts (pockets) in the light organ
- bacteria accommodate crypt, dusts constrict and fields of cilia waste away, light organ matures
How does the LuxI-LuxR Quorum sensing system regulate the light producing genes?
1) LuxI (enzyme) produces autoinducer molecules called homoserine lactone that diffuse out of cell
2) once in high enough concentration the autoinducer binds to LuxR partner protein
3) binding of LuxR and autoinducer causes DNA binding domain on LuxR to be unveiled allowing the complex to sit at the gene promoter of the CDABGE operon
4) (aka. formation of this complex activated transcription of the LuxICDABGE operon)
5)
- causes Lux proteins to be made
- LuxA and LuxB genes code for alpha and beta sub units of luciferase that catalyses a redox reaction that produces blue-green light
- LuxC,D and E code for components of the fatty acid reductase complex requires for the synthesis of the aldehyde substrate for luciferase
- LuxG thought time code for flavin mononucleotide reductase that generates reduced flavin mononucleotide as a substrate for luciferase
*this mechanism is on gram negative bacteria
Operon
Functioning unit of DNA containing a cluster of genes under the control of a single promoter
What was something interesting from the MOOC ‘An Introduction to Microbiology’?
Photosynthetic bacteria ???
Explain how coral symbionts transform from mutualists to opportunists due to excessive DOC
Mutualist - both species gain benefit
Opportunist - non-pathogenic organisms that act as a pathogen in certain circumstances
Algae produce DOC (dissolved sugars and carbohydrates in water) - nourish microbes of coral - microbes grow and consume surrounding oxygen - coral suffocates
Opportunistic
How does C.Difficile shift from a mutualistic to pathogenic state in the gut?
mutualism:
C.difficile: gram positive bacteria
- C. difficile gain hospitable environment in gut (warmth, nutrients)
- member of normal gut microbiome but growth is suppressed by other more dominant anaerobes
- part of our normal gut microbiome (which has known benefits ie. promoting innate and adaptive immunity)
Pathogenic process: depends on whether C diff can colonies and the colonization resistance of the gut microbiome.
Infection caused by: commensal microbiota which creates a barrier effect is lost following anti microbial therapies (use of antibiotics). Allows C diff to colonies in intestine.
Interaction of C.diff and intestinal epithelial cells* and begins a cascade of inflammatory processes that contribute to intestinal diseases such as diarrhea and pseudomembranous colitis.
epithelial cells intoxicated with C. Difficult release proinflammatory mediators including interleukin 8 and macrophage inflammatory protein 2 into the lamina propria (thin layer of connective tissue lining GI tract) that initiates an acute intestinal inflammatory response
Alterations in normal gut microbiome provides a new niche for C. Diff to colonies in
What else did you discuss with Dr Knox that was interesting?
- norovirus respiratory virus outbreaks
- C. Difficile came about after poor use of antibiotics, massive outbreak at end of 1990s
- cytotoxicity - how does C. Difficile actually cause disease ?
IGA mucosal immunity
Childhood colonisation is common but childhood disease is not.
MRSA
selective pressure in the hospital setting
Bacteria - epigenetics ?
Gut microbiome and immunity
Bacterial recognition systems
Hepatitis C looking at cellular responses
BZV
Stafforius
Registra ?
Going through blood cultures that come up positive
Was going to shadow her in the laboratory
Looking at culture plates discussing cases
Do a bench round
Pregnancy and neonatal infections
Shumaila:
Faecal transplants
How did you challenge the data on the abundance of C. Difficile in the GI tract?
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- found some alternative articles that suggested C. difficile increase may be due to ?
How did you analyse the data on C.difficile’s abundance in the GI tract?
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- looked at some graphs of its abundance upon antibiotic use
- clearly abundance increased
- linked that to the deteriorating barrier effect of commensal bacteria
Graphs:
Comparing sample from patient and normal person
Before antibiotic treatment,
Klebseilla bacteria - UTI
colours = species
Telling you how many of each species is there
Ackermamansia predominant before treatment
Succession ?
After they added antibiotics, C. Difficile hasn’t grown
May have used narrow spectrum antibiotics only for gram positive bacteria so didn’t target C. Difficile
C. Difficile negative, C. Difficile positive. Colour coding = different pathogens
C. Difficile = gram positive
Why do 70% people not get affected by C. Difficile? Depends on environment, our community, immune system
Microbial forensics
Microbiomes are different in C. Difficile positive and negative people
Bacterial richness
Read the summary of what the graph is apparently showing, read the bit of the paper, see it as a whole
Tuberculosis - screened different genes wanted to know which are specific to mycobacterium and which were not. Clones genes into vectors and developed new vaccines for TB.
PCG vaccine
Note - ask interviewer what the most interesting thing they have ever discovered or learnt about ?
Explain how gut dysbiosis, rather than mutations associated with the SHANK3 gene is a cause of autistic behaviour.
bi directional communication between the gut and brain - connected by the vagus nerve
gut microbiome influences our brain and hence behaviour
- effects of probiotics on autistic symptoms
- substances secreted by microbes can infiltrate blood vesels
- microbes prompt neuropod cells lining the gut to stimulate the vagus nerve that connects to the brain
- microbes activate enteroendocrine cells in gut lining which send hormones throughout the body.
What else did you discuss in you essay titled ‘to what extent is human behaviour genetically determined’?
Amino acid tryptophan, which some gut bacteria produce, could be a causal link.
Microbes convert tryptophan into serotonin
(a neurotransmitter implicated in depression and other psychiatric disorders)
Cells also turn tryptophan into a substance called kynurenine, (reacts further to form products that can be toxic to neurons)
Changes in the microbiome might tip the production of kynurenine and tryptophan in a way that impairs mental health
Research has shown: people with depression convert tryptophan into kynurenine more readily than into serotonin. (more K means more toxicity to neurons)
What about your essay do you think made it come runner up?
500 words
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What motivated you to complete the MOOC ‘An Introduction to Cancer biology’?
- uncle
- telomeres ?
- interests din cells so made sense ???
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Explain how cancer evades the immune system via the PD-1/PD-L1 complex
- Immune checkpoints: prevent immune responses from damaging healthy cells
- PD-L1 - protein that in humans is coded for by the CD247 gene - on tumour cell
PD-1 - protein on surface of T-cells
PD1 and PD-L1 = immune checkpoint proteins
Anti-PD-1 and anti-PD-L1 = immune checkpoint inhibitors
binding of PD-1 and PD-L1 results in tumour cell not undergoing apoptosis. Cancer cells upregulate PD-L1 to avoid cell death.
So checkpoint inhibitors administered, anti-PD-1 binds to PD-1 and anti-PD-L1 binds to PD-L1 preventing interaction of PD-1 and PD-L1
Normally : interaction of PD-1 and PD-L1 results in T cell immune suppression
Does cancer evade the immune system in any other way?
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CTLA-4
What was something else that interested you in the MOOC ‘Am Introduction to Cancer Biology’?
(telomeres)
OR
Warburg effect
most cancer cells:
predominantly produce energy by a high rate of glycolysis followed by lactic acid fermentation in the cytosol
RATHER THAN
low rate of glycolysis followed by oxidation of pyruvate in mitochondria (as in most normal cells).
Two hit hypothesis ?
10 hall marks ?
How did you explore the mechanisms of the PD-1/PD-L1 complex further whilst reading ‘The Immunotherapy Revolution’?
I read about a similar mechanism involving CTLA-4 where when CTLA-4 is bound to a B7 protein it inactivates T cells and prevents them from killing cancer cells.
- TCR binds to MHC and antigens on APC,
CD28 (on T cell) binds to B7-1/B7-2 on the APC,
YES BINDING OF B7-1/B7-2 to CTLA-4
= inactive T cell = NO cancer cell death - TCR binds to MHC and antigens on APC,
CD28 (on T cell) binds to B7-1/B7-2 on the APC,
NO BINDING OF B7-1/B7-2 to CTLA-4 (blocked with anti-CTLA-4)
= activated T cell = cancer cell death
cancer cells hijack macrophages and expresses B7 protein which CTLA-4 on T cell binds to and makes the T cell inactive
What was something else you found interesting in ‘The Immunotherapy Revolution’
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Define CAR T-Cell therapy
Genetic engineering of a T cell to possess an artificial chimeric antigen receptor that can target a specific antigen of a cancer or tumour cell
Why do you believe CAR T-Cell therapy is crucial in our fight against cancer?
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