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Molecular and Cellular Biology:Exploring the Architecture of Life
Marc Coppolino
Department of Molecular and Cellular BiologyUniversity of Guelph
Molecular and Cellular Biology
Tariq AkhtarEmma Allen-VercoeMark BakerAndrew BendallManfred BrauerMalcolm Campbell Anthony Clarke Joseph ColasantiMarc CoppolinoGeorgina CoxJohn DawsonMichael EmesSteffen GraetherGeorge Harauz
Nina JonesDavid JosephyAzad Kaushik Cezar KhursigaraMatthew Kimber Jasmin LalondeRay Lu Jaideep Mathur Baozhong MengRod MerrillRichard MosserRobert Mullen Lucy Mutharia
Annette NassuthMelissa PerreaultSteven RothsteinScott RyanStephen SeahRebecca ShapiroIan TetlowJim UniackeGeorge Van der MerweTerry Van RaayJohn VesseyChris WhitfieldKrassimir Yankulov
BiochemistryMicrobiology
Molecular BiologyAnd Genetics
Molecular and Cellular Biology
Botany
Neuroscience
Molecular and Cellular Biology
Tariq AkhtarEmma Allen-VercoeMark BakerAndrew BendallManfred BrauerMalcolm Campbell Anthony Clarke Joseph ColasantiMarc CoppolinoGeorgina CoxJohn DawsonMichael EmesSteffen GraetherGeorge Harauz
Nina JonesDavid JosephyAzad Kaushik Cezar KhursigaraMatthew Kimber Jasmin LalondeRay Lu Jaideep Mathur Baozhong MengRod MerrillRichard MosserRobert Mullen Lucy Mutharia
Annette NassuthMelissa PerreaultSteven RothsteinScott RyanStephen SeahRebecca ShapiroIan TetlowJim UniackeGeorge Van der MerweTerry Van RaayJohn VesseyChris WhitfieldKrassimir Yankulov
bacterial surfacesProtein structure and function
Host-pathogeninteractions
Cancer biology
Human gut microbiome
Stress response in yeast
Virology
Developmental/Cell biology
Plant metabolism
Eukaryotic signaltransduction
Molecular and Cellular Biology
Neuroscience of agingand disease
In MCB, researchers strive to understand how cells work. By examining the molecules that make up cells, we will ultimately understand the inner workings
of the basic unit of life - the cell.
Our primary motivation: DISCOVERY
The molecular basis of cells is common to all life
The Prokaryotic Cell (e.g bacteria)
The Eukaryotic Cell(e.g. human liver cell)
Cells… many shapes many sizes many interactions
This gives rise to emergent (and most amazing!) properties of life…
Multicellularity
Interactions between cells, and betweencells and their environment, are thefoundation of multicellular life
What determines and maintains the architecture of cells, tissues and organs?
Examples of Research in MCB
Cezar Khursigara- Bacterial cell division target for novel antibiotics
Tariq Akhtar- Analysis of secondary metabolites in plants
Terry Van Raay- Developmental mechansims in Zebrafish
Matt Kimber- Bacterial proteins involved in CO2 fixation
Rebecca Shapiro- Genomic approaches to study fungal pathogens
George Van der Merwe- Regulation of fermentation in wine yeast
Dr. Nina JonesCellular Interactions that Regulate Kidney Function
glomerulus
podocytes
A protein called ‘nephrin’ allows connections between podocytes in the kidney - forming a filter
In many kidney diseases, disruption of nephrin function impairs filtration
The Role of Brain Waves in Communication within the Central Nervous System
Dr. Melissa Perreault
Alterations to brain waves are associated with several disorders, for example: Alzheimer’s disease Schizophrenia Depression
What are brain waves?
Rhythmic, repetitive electrical impulses in a group of neurons cause ‘waves’.
Brain waves result from rhythmic or repetitive neural activity
CRUCIAL TO BRAIN COMMUNICATION Changes in brain wave patterns at specific
frequencies contribute to a number of central nervous system diseases
Brain wave
What are brain waves?
In humans, brain waves can be taken through the scalp EEG
Animal models are an essential tool to further our understanding of brain functions
• Unlike humans, brain waves from many regions can be assessed observe broader, brain-wide activity
• Drug-effects ex. antidepressants, antipsychotics• Timelines are possible for early-to-late stage disease• Correlations of brain wave patterns with behaviour
Mood disorders Addiction Obesity
Diseases such as Alzheimer’s, schizophrenia, and depression are associated with altered brain wave patterns that contribute to cognitive dysfunction
Depression: lifetime prevalence of ~15% in Canada; twice as common in women
Current antidepressant therapies are limited
Characterized by asymmetries in brain waves between left and right frontal cortex
Involves function of specific molecules(e.g. proteins serotonin receptor)
What can we learn about cognitive function from studying brain waves?
1. Are there innate sex differences in brain wave patterns?2. Can brain wave patterns predict depression susceptibility? 3. Can these patterns be used to identify novel therapies?
Dr. Scott RyanInvestigating the cellular basis of neurological disorders
e.g. Parkinson’s disease
Parkinson’s Disease
Parkinson’s disease is characterized by accumulation of aggregated proteins in brain cells
Leads to cognitive decline Brain has limited capacity to
generate new cells
Production of cells in tissues is carried out by stem cellsStem Cells – can divide indefinitely, make multiple cell types, and exists for the life of the organismCan Parkinson’s disease be treated with stem cells?
Adult brains have limited capacity to produce more brain cells!
How can we get more stem cells?
Molecular and cellular technologies can be used to generate stem cells
* Specifically for individual patients
biochemistry of bacterial toxins involved in disease
Dr. Rod MerrillBiochemical analysis of bacterial toxins and their role in disease
Many bacteria produce toxins that are deadly to cells These toxins are released by bacteria, so even if the
bacteria are eventually eliminated, the toxin can persist Presents many challenges to fighting infection
e.g. cholera, whooping cough, agricultural diseases
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Apis mellifera (European honey bee)
• Originally domesticated for honey
• Contribute to global food stores
• Declining populationsParasitesDiseases
American Foulbrood
• Causative agent: Paenibacillus larvae
• Targets the brood of the colony
(Modified from Müller et al., 2015)
American Foulbrood
(Simon et al., 2014)
P. larvae produces a protein toxin (C3larvin) very similar to that of Vibrio cholerae
ADP-ribosyltransferase (enzyme) These toxins enzymatically alter proteins in
infected cells kills cells
Using chrystallography, structural proteomics, and biochemistry, Dr. Merrill’s group is working to identify ways to block the toxin
Cell Migration and invasionin tumour progression
Marc Coppolino
Department of Molecular and Cellular BiologyUniversity of Guelph
Abnormal cell movement drives the spread of cancer
Malignant tumour cells invade neighboring tissue
In tissues, cells exist, and move, within a 3-dimensional environment
- surrounded by external protein matrix
Cell
ExtracellularMatrix (ECM)
Tumour cell invasion requires enzymes that breakdown the protein matrix outside cells.
Tumour cells secrete theseenzymes
invadopodium
t-SNAREs
MT1-MMPMMP
integrin
Degradation of the matrix is a highly organized process- structures calledinvadopodia
These structures can be studied biochemically and microscopically
Src EGFRTks5 overlay
Src F-actinEGFR overlay
Invadopodia as seen under the microscope
F-actin overlayY845-EGFR zoom
What cellular components are required for cancer cells to invade other tissues?
How do invadopodiaform?
invadopodium
t-SNAREs
MT1-MMPMMP
integrin
MT1-MMPF-actin
Control
overlay
shRNASNAP23
GFP
shRNASyntaxin4
SNARE proteins are required for the formation of invadopodia
Ultimately, we hope to stop tumour cells from doing this, in order to prevent this
Molecular and Cellular Biology
Discovering the cellular and molecular architecture of life….
Thank you!