Challenge in life Flashcards
1
Q
The world is in big trouble
A
- From a geological time perspective, CO2 levels are far too low and the earth is far too cold.
- For much of plant evolutionary history, atmospheric CO2 levels were above 1000 ppmand not limiting for growth of most plants
- CO2 concentrating mechanisms in plants evolved within the last 65 million years in response to decreasing levels of atmospheric CO2
- Currently, atmospheric CO2 levels are in the midst of a rapid and dramatic increasing, starting with the industrial revolution
2
Q
Impact of increase in C02 pressure
A
- The direct impact of increasing atmospheric [CO2] will be on plants, through changes in rainfall patterns, temperature, and distributions and interactions with beneficial and harmful organisms
- Plants grow better at higher [CO2], although often show decreases in proteins and nutrient level
3
Q
Problem with photosynthesis at high temperature
A
Two competing reactions, Carboxylation and Oxygenation
• Oxygenation (Photorespiration) product has to be recycled, which is energy-dependent and releases CO2.
4
Q
C4 photosynthesis
A
- evolved more than 60 times, mainly in hot, dry regions
- C4 photosynthesis is advantageous in dry, hot and sunny regions
5
Q
Pathway of c4 plant
A
- Atmospheric CO2 enters mesophyll cells and is converted to bicarbonate. PEPC carboxylates PEP to produce OAA, a four-carbon compound
- OAA (or a derivative) is transported to a bundle sheath cell and decarboxylated, releasing CO2 at Rubisco, which initiates the Calvin-Benson cycle. A three-carbon compound returns to the mesophyll cell.
6
Q
C3 vs C4
A
- C3 plants have an advantage at cool temperature (the additional carboxylation steps of C4 require energy)
- Because photorespiration increases with temperature, C4 plants have an advantage higher temperatures
- Because carbon-fixation in C4 plants is not carbon-limited, they are able to take advantage of high light intensities
7
Q
C4 phylogeny
A
There are ~8000 species of C4 plants, clustered into ~61 unique lineages
27 monocot lineages represent ~6000 species
~34 dicot lineages represent ~1700 species
8
Q
enzymes required for C4
A
All enzymes required for C4 pathway are in C3 plants
This means two things: 1. It has been relatively easy for plants to acquire the capability for C4 photosynthesis from the ancestral C3 state
2. It could be feasible to engineer features of C4 photosynthesis in C3 crop plants like rice and soybean
9
Q
C4 Requires a change in plant leaf
A
• Changes in leaf anatomy (higher ratio of bundle sheath to mesophyll cells)
• Functional differentiation between bundle sheath to mesophyll cells, changes in gene expression
• Changes in plastid function and position
-Two compartments, separate but close enough for metabolite exchange
10
Q
Crassulacean Acid Metabolism (CAM)
A
- CO2 uptake at night (less water is lost through open stomata at night)
- HCO3- is fixed by PEPC
- CO2 is stored as C4 acids in the vacuole
- Daytime decarboxylation releases CO2
- Rubisco fixes CO2 during the day, even though stomata are closed
11
Q
Crassulacean Acid Metabolism (CAM) vs. C4 metabolism
A
- C4 provides benefits under high temperature, high light & high water availability
- CAM provides benefits under high temperature and low water availability
12
Q
Many plants have “facultative CAM” properties
A
-Plant can ultilise CAM when there is a drought
13
Q
Transgenic manipulations in response to [CO2]
A
- Modifications to Rubisco or other enzymes used in CO2 fixation
- Engineering CAM to improve water-use efficiency
- Strategies to improve C4 photosynthesis
- Producing different enzymes with enhanced properties
- The C4 rice project
- Convert a C3 plant to a C4 plant
14
Q
Turbocharging rice: the C4 rice project
A
• Started in 2008.
• Seven institutions involved.
• Two step process: change both biochemistry and plant anatomy through genetic engineering.
• Creating a line with five enzymes altered took six years
. • Also have to manipulate expression of transporters.
• May not be able to develop the Kranz cell types (but that may not matter).
15
Q
pathogen
A
A pathogen is “a disease-causing microorganism”
16
Q
disease
A
disease is “any condition in which the normal structure or function of the body is damaged or impaired
17
Q
evolution of immunesystem
A
Immune systems are evolutionary ancient, and become increasingly complex over evolutionary time
18
Q
Phase of immune respond
A
• An immune response has three broad phases
- Recognition phase—organism must discriminate between self and non-self
- Activation phase—mobilization of cells and molecules to fight the invader
- Effector phase—mobilized cells and molecules destroy the invader
19
Q
Components of the (mammalian) immune system
A
- In multicellular animals, the immune system functions through a variety of specialised cells
- Nonspecific “Innate” immune response • acts as a first line of defence against pathogen/agent
- lacks immunological memory (?)
- Specific “Adaptive” immune response
- resistance to a particular foreign agent
- has “memory”; effectiveness increases on repeated exposure to agent
- Cells with similar functions exist in other organisms
20
Q
Step 1: Recognising pathogens
A
• All immune responses begin with the recognition of foreign agents/pathogens by specialized receptors present in cells
• These are known as PRRs: Pattern Recognition Receptors
There are 4 of them
-CLR
-NLR
-TLR
-RLR
21
Q
CLR
A
C-leptin receptor
- transmembrane receptor found in the plasma membrane
• Recognise fungal and bacterial glycans (sugars)
22
Q
NLR
A
NOD-like receptors:
• Cytoplasmic receptors
• Different subfamilies recognise different foreign molecules from viruses, bacteria, parasites and fungi
23
Q
TLR
A
Toll-like receptor
transmembrane receptor found in either the plasma membrane or the endosome
• Different TLRs recognise different molecules
• Toll-Like Receptors are found in both vertebrate and invertebrates
• Different TLRs recognise different PAMPs (?); mammals have at least 10 TLRs
24
Q
RLR
A
Retinoic-acid-inducible gene 1-like receptors:
• Cytoplasmic sensors of viral RNA
• Trigger antiviral responses
25
MAMPs
Microbial-Associated Molecular Patterns (molecule that doesnt orriginate from our body)
26
So what patterns, exactly, are they recognising
• MAMPs: Microbial-Associated Molecular Patterns
-Pathogen
• Carbohydrate, polypeptide, and nucleic acid molecules expressed by viruses, bacteria, and parasites:
• DAMPs: Damage-Associated Molecular Patterns
• Signals of damage to an endogenous cell by a pathogen
• Can include: Membrane damage Molecules released by stressed, dead or dying cells Signals of tissue damage • MAMP in wrong place or MAMP+DAMP = PAMP
• PAMP: Pathogen-Associated Molecular Patterns
• Sensing of PAMPs by cells of the immune system (through their PRRs) sets off the next stage of the immune response
27
Step 2: Activation of the immune response
• PAMP sensing by PRRs leads to:
1. Secretion of defensins or other antimicrobial peptides
2. Production of pro-inflammatory cytokines 3. Activation of the complement system
4. Phagocytosis
• All of these responses are non-specific and part of the innate immune response
5. Targeted responses to specific threats by the adaptive immune response... but this takes days or weeks
28
Defensins
* Secretion of defensins, a type of antimicrobial peptide is an ancient form of defense
* Small, positively charged polypeptides (< 100 AA)
* Bacteria secrete "bacteriocins" which have equivalent roles
* Defensins disrupt the structural integrity of pathogen membranes and (some) viral envelopes
29
Phagocytosis: disposing of pathogens
* Once pathogens have been disrupted or identified, they must be removed from the cell
* Phagocytosis: The process in which a cell encloses large particles in a phagocytic vacuole (phagosome) and engulfs them.
30
after phagocytosis
• Two main consequences to phagocytosis: 1. Activation of a pro-inflammatory response, to recruit additional immune cells to the site of injury/threat
2. Activation of the adaptive immune system by antigen presentation to T and B cells
31
Antigen presentation by phagocytes links the innate and adaptive immune response
- Microbes are broken down by phagocytosis
- the phagocyte carry microbial peptide to lymph nodes
- This cause the activation of specific t-cell
32
B cells and T cells are the main players of the adaptive response
* Each B and T cell clone recognises different antigens
* An antigen is simply "a molecule that can induce an adaptive immune response or that can bind to an antibody or T cell receptor."
* At any time, many different B and T cell clones circulate through the body, but low cell numbers of each clone
33
Type of t-cell
Produced in the thymur
• Each B and T cell clone recognises different antigens
• An antigen is simply "a molecule that can induce an adaptive immune response or that can bind to an antibody or T cell receptor."
• At any time, many different B and T cell clones circulate through the body, but low cell numbers of each clone
34
Type of B cells
-Produced in the bone marrow
-B cells secrete antibodies and mark pathogens for destruction
-• Antibodies bind tightly to their target pathogen, inactivating it or marking it for destruction by phagocytosis or complement-induced lysis.
• After encountering their specific target antigen, some B cells will become long-lived memory B cells • Secondary exposure to this target will result in a faster, more intense immune response
35
The components of the immune system function cooperatively
• The adaptive immune response requires time (days to weeks) to be effective:
1. The right T and B cell need to recognise the pathogen
2. T and B cells clones need to expand/proliferate
3. T and B cells need to neutralise the threat
• There is a clear role for the (rapid, non-specific) innate immune system in mitigating threats.
36
The diversity of T and B cell receptors and antibodies
The diversity of T and B cell receptors and antibodies is generated through V(D)J recombination
• The genome of each B and T cell undergoes random rearrangement of a set of regions known as V, D, and J, all of which are part of the genes coding for antibodies
• Different V, D, J combinations = different antigen binding sites = different antigens recognise
37
Comparisons between animal and plant immunity
* Animals have
* Basal innate immunity
* Innate complement response
* Adaptive immune response (antibodies & specialized cells)
* Plants have
* No circulating antibodies or cells • Structural barriers: cuticle, cell wall
* Basal innate immunity = Pathogen Triggered Immunity (PTI) Mediated by the equivalent of a PRR
* Effector Triggered Immunity (ETI); often ‘gene for gene’ interaction Mediated by different receptors
* Adaptive systemic signals emanating from infection sites (Systemic Acquired Resistance) • Toxic molecules, programmed cell death
38
Bacterial adaptive defences: The CRISPR system
* CRISPR: Clustered Regularly Interspaced Short Palindromic Repeats
* Infection from phage or similar is recorded in CRISPR array and expressed in subsequent infection
* Two components: CRISPR array and Cas protein • Cas marks targets for destruction by bacterial cellular machinery
39
What cause diesies
* Most infectious diseases are caused by a single pathogen. • (Different pathogens for different diseases, obviously!)
* But imbalance in the microbial communities in our bodies (eg gut microbiome) can be associated with some diseases • Examples: autoimmune and allergic diseases, obesity, inflammatory bowel disease, diabetes, depression... • Link is not very well understood
40
Types of microbes that cause disease
* Viruses
* Bacteria
* Protists
* Fungi
* Other animals
* Any lineage except for Archaea
41
Viruses
* Infectious agent
* Not cellular
* Cannot reproduce by itself
* Needs a host cell to make copies of itself
* Comprised of a genome (DNA or RNA), capsid (protein) and sometimes a membrane (lipid)
* No ribosomes, organelles, energy metabolism
* Small (nano- rather than micrometre scale)
42
Bacteria
* Lack a membrane-bound nucleus, organelles, and cytoskeleton
* Different cell walls (peptidoglycan in bacteria)
* Gram stain is used as a broad way to differentiate bacteria based on cell wall structure.
* Penicillin targets peptidoglycan.
* Different rRNA sequences
* Therefore different ribosomes (antibacterial targets)
43
Parasitic protists
* Eukaryotes
* Cause a suite of diseases, including Giardia, Chagas disease, African sleeping sickness, toxoplasmosis, malaria
* Limited treatment options because like us, they are eukaryotes
44
Fungi
* Fungi are one of the most common diseases in people (e.g. dandruff, yeast infections, toe nail fungus)
* A number of species are also able to kill people
* Invasive fungal infections kill more people than TB or malaria
* 150 people die an hour from fungal diseases. • Usually in immunocompromised people or complications from other diseases.
45
How do pathogens cause damage to the host?
* Common elements for microbial diseases are:
* Colonise a host
* Grow within the host
* Evade host immune system and defense
* Damage the host
* Leave the host
* There are numerous mechanisms by which damage is done.
46
Why do pathogen damage host
REPRODUCTION AND SURVIVAL
47
host-microbe interactions
* Mutualism: both the microbe and host benefit.
* Gut microbiome, everyone wins
* Commensalism: the microbe benefits but offers no benefit and causes no harm
* Many viruses have no noticeable effect on our health
* Parasitism: the microbe benefits to the detriment of the host, as is often the case for pathogens.
48
Type of pathogen
Primary pathogens...
• can cause overt, immediate disease in most healthy people
Asymptomatic cases...
• may persistently infect a single individual for years without causing overt disease •
Opportunistic pathogens...
• cause disease only if immune systems are weakened
49
The damage response framework
* The health outcome to the host is an interaction between the microbe and the host’s immune response.
* Microbes can cause disease with either level of immune response.
* Overactive immune responses can cause disease in the absence of a pathogen, e.g. allergies and autoimmune diseases
50
Virulence
severity of harmfulness of a disease or poison
51
Host and Pathogen battle
* Hosts are interested in defending against pathogens
* Pathogens cause disease and decrease a host's ability to reproduce
* Pathogens are interested in infecting hosts • Obligate parasite, easier access to nutrients...
* These two interests are incompatible, and place host and pathogen in direct conflict with each other • Direct... and endless
52
Drug resistance: the microbes winning the battle
* Resistance can emerge to many drugs, as microbes mutate and therefore the chemicals no longer function.
* Some microbes (especially bacteria) have enzymes that degrade antibiotics.
* Lots of chemicals are antimicrobial in nature; the trick is finding one that does not also kill the host.
53
Resistance can move between some bacteria easily
• Bacteria may have specific genes to break down antibiotics, often carried on small pieces of DNA (plasmids). • These plasmids or fragments of they can move between species
54
Why do some vaccines fail
* There is variation between microbe strains
* Or... some modify their appearance quickly (e.g. Trypanosoma)
* Or... They target immune cells specifically (e.g. HIV)
* Or... few antigens are available that induce a protective response
* Or... people’s immune systems vary
55
Antimicrobial chemicals
* Must inhibit or kill the microbe but not the host.
* Usually work by inhibiting as aspect about the microbe’s biology that is unique, not found in humans.
* Discovery through: • (1) Massive chemical screens • (2) Luck and then hard work • (3) Screening microbes (and plants) for active agents • (4) Traditional medicine for clues
* Natural products may now be synthesised, or modified to improve their properties.
56
What is cancer?
* Cancer refers to a (large) group of diseases with different properties and prognoses, but two unifying commonalities:
* All cancers are caused by unchecked cell proliferation and have the ability to invade other tissues
* Types of cancer: • Hereditary cancers • Sporadic (non-hereditary) cancers • Transmissible cancers
57
Hereditary and nonhereditary cancers
Although some cancers and cancer risks are hereditary (retinoblastoma, some types of breast cancer), the vast majority of cancers are sporadic and caused by somatic mutations
58
Cause of cancer
• Maintaining cell numbers requires balancing cell death and cell birth. • When these processes become decoupled tumours are formed
59
Cancer is a genetic disease
• Dysregulation of multiple cellular mechanisms is necessary to give rise to cancer.
-cell proliferation, DNA dmg respond, cell growth, cell survival
Together, all these changes give rise to genetic instability and sustain the cancer phenotype (unchecked growth, invading tissues)
60
Genetic instability is a hallmark of cancer
• The karyotypes of late-stage cancers reveal extreme genetic instability, with widespread chromosomal gains, losses and rearrangements
61
Two major classes of genes are mutated in cancer genes
1. Tumour suppressor genes (recessive)
2. Dominant oncogenes • (Oncogenes are mutated forms of normal proto-oncogenes)
• In either case, mutations may cause
• over-expression of the gene product
• aberrant activity
• imitation of normal growth and death signals
62
What are tumour suppressor genes?
* Tumour suppressor genes often have roles in cell cycle control or the DNA damage response
* Checkpoint genes such as cyclins, CDKs and others, control the transition from one cell cycle phase to the next
63
What happens when a checkpoint fails
* p53 is a G1 checkpoint sensor, always expressed in cells
* When it senses DNA damage it stimulates production of p21
* p21 binds to G1 CDKs, preventing their activation and stopping cycle progression
* If damage is too severe to be repaired, the cell will undergo apoptosis
* p53 is a key sensor of DNA damage, mutated in roughly 50% of cancers
* Loss of a single copy of p53 is not enough for a cell to lose its damage sensing properties
* Mutations to both copies are needed before loss of p53 function.
64
Dominant oncogenes
* These mutations are dominant because they often lead to the constitutive activation of genes • (but there's a tradeoff)
* Proto-oncogenes have different functions from tumour suppressors • Stimulate cell growth • Inhibit cell death or terminal differentiation
65
Subverting signalling cascades
* Genes in growth signalling pathways are often proto-oncogenes • These pathways respond to external stimuli (growth factors) by setting off a cascade of signalling that leads to cell growth and division.
* Mutations cause pathway components to be constitutively active
* Proliferation continues even in the absence of the growth factor signal
66
how many mutations does it take to get cancer
* One or two mutations are not sufficient to get cancer.
| * Mutations have to accumulate across many genes for a cell to become oncogenic.
67
Peto's paradox: what's up with big animals and cancer
* Large animals are 1. made of many cells (in the order of quatrillions) 2. long lived
* Most animals have 2 functional p53 alleles.
* Two different research groups have shown that elephants (and extinct mammoths) have (had) up to 20 copies of the p53 gene
* Their cells are far more capable of tolerating DNA damage!
68
What causes transmissible cancers?
• Up to 15% of cancers are caused by viruses or other infectious microbes.
• This includes the Human Papilloma Virus and cervical cancer, as well as an association between hepatitis B and liver cancer in Africa and Southeast Asia
• These microbes infect cells and hijack the cellular machinery, causing cells to proliferate and become cancerous.
(
69
Why does cancer develope late in life
• Developing cancer requires accumulating multiple mutations . This takes time
70
Our environments impact our cancer risk
* Different behaviours and environments expose individuals to different carcinogens and mutagens
* The decrease in stomach cancer and rise in lung cancer are both associated with behavioural shifts
71
Impact of weeds and introduced species
* A weed is a ‘plant growing in the wrong place’ • Usually opportunistic species, e.g. blackberry, Bitou bush
* May grow rapidly and provide cover for foxes, rabbits or other introduced species
* The ‘interconnectness of life”
* May degrade native animal habitats
* Ornamental (garden) species can become weeds if they spread into native bush
72
Cane toads
• Introduced into Australia in 1935 to control the cane beetle, because of success in Puerto Rico.
• But they don't eat cane beetles at the top of sugar cane because they cannot climb well
also very poisonous
73
Amanita muscaria
* Forms mycorrhizal relationships with the roots of plants. • Introduced to improve Australian pine plantation.
* Spread to native plants, displacing the native fungal species.
74
Many introductions were inadvertent
* Ballast water from ships
| * Microbes
75
Indigenous land managment practices
* Indigenous communities have long practiced multiple kinds of land management and shaped the Australian environment
* Many of these practices ceased following European colonisation
76
Periodic burning in Australia maintains biodiversity
* As a consequence of natural and long-tern Indigenous fire use, many Australian plants are specifically adapted for fire.
* Patchwork burning in early fire season thins out young shrubs and trees while preserving the canopy and encouraging growth of new grass. • Contrast to the effect of intense late season fires, or even prescribed burns
77
Human impact on the environment
- 83% loss of wild animal
- 80% loss of marine animal
- 50% loss of plant
- 15% loss of fish
78
The invention of agriculture
Domestication of plants and animals occurs in multiple sites worldwide beginning 10,000 years ago.
79
What is domestication?
* Domestication involves one species controlling the reproduction and breeding of a second species, generally to its own benefit
* Humans have domesticated ~50 species of animals and thousands of plant and fungal species
80
Domestication of plant
- In plants, domestication is often associated with hydridisation and/or increased numbers of chromosomes
- Durum wheat (Triticum durum) is a tetraploid
- Bread wheat (Triticum aestivum) is a hexaploid
81
Domestication syndrome in animals
• The domestication of animals is often associated with a suite of morphological and behavioural changes
• This observation suggests a few things about how domestication actually happens
• Domestication of most animals is often hypothesised to have selected for one trait at first: tameness
• But tameness is a complex trait, there's no "gene for tameness"
• Tameness seems to be a by-product of cells from the neural crest
-Change in the neural crest also cause morphological and reduce fore brain size
• No consistent set of traits defines domestication, at least in experimental systems trying to reproduce the process.
• Although most domestic animals present a subset of traits associated with the syndrome
82
Domestication syndrome in plants
* Early domestication of plants selected for morphological and physiological traits
* Reduction (or increase) in anti-herbivory molecules, different pigmentation, seed pods that do not shatter, larger fruit…
83
HOW does domestication happen
* Domestication entails selection for specific traits
* This leads to an initial loss of genetic diversity in the species being domesticated, as variation is removed from the population
84
zoonoses
Zoonoses are diseases transmitted from animals to human
• Domestication, combined with higher population densities in settled agriculturalists, was a hotbed of zoonotic transmission
• (only our recent control of infection disease has really mitigated this problem
• Zoonoses account for: • 60% of all infectious diseases in humans • 75% of emerging infectious diseases in humans • COVID19 is just the latest example
• Political decisions, intensive farming practices and erosion of wild land all will continue to contribute to the problem
