BIOL6193 - Colloquium in Molecular and Cell Biology
Proteins bind to the UTR
RNA structure mimics a snake eating it's tail when it's being transcribed
RNA Control Permeates Pain
Dorsal Root ganglion (DRG)
They have interesting axons
One goes into spinal cord
One goes all the way to extrimites
It would take days to move RNAs from the center to the distal locations.
5% bind to the DNA
Which RBPs contribute to plasticity?
Does the Poly A Binding Protein(PABP) play a role?
It's expressed in DRG
Dr. Lin Jia
Obesity-associated Low-grade Inflammation
Inflammation leads to insulin resistance
Insulin Resistance and glucose control
Liver glucose production decreases
Muscle and adipose uptake increases
Live glucose production increases
Muscle and adipose uptake decreases
Toll-like Receptor 4 (TLR4)
created floxed mice
Tested mice for glucose tolerance
Alcohol and Liver inflammation
Endotoxemia and AALD
moderate to severe
surgery, Liquid diets
Alcohol in the drinking water
pair feeding and liquid diets
Increase in fats in liver
Increase in cytokines
#1 Role of hepatoctye TLR4 in alcohol and insulin resistance
#2 Risk Factors in AALD
#3 Tissue-specific Lipogenesis in AALD
#4 Adipose Tissue Lipolysis in AALD
#6 Exercise and AALD
Running mice with alcohol had significantly less lipid content
Please list four risk factors that will affect the development of alcohol-associated liver disease.
Gender, Genetics, drinking pattern, obesity.
Dr. Jyoti R. Misra
Organisms grow to a predictable size
Hippo pathway is a conserved regulator of growth
Mis-regulated in most cancers
Dachsous-Fat signaling regulates growth through the Hippo pathway
Disruption of planar cell polarity affects organ shape
Results in shorter fatter wings
Gal4-UAS systme for transgene expression
Started cutting out around 30 min
Treatment with Choloroquine increases stability of Fat and Fat4. This means these proteins are degraded by _?
Dr. Nikki Delk :cancer:inflammation:breast-cancer:prostate-cancer:
Androgen Receptor drives PCa
BCa & PCa Develop Resistance to Hormone & HR-Targeted Therapy
Other types of cells besides just tumor cells
Take advantage of immune cell factors to help them survive
Expose cancer cell lines to IL-1 acutely
Creates a subline from Chronic IL-1
They develop IL-1 insensitivity
Represses HR(hormone receptors) accumulation/activity
Inflammation drives breast and prostate cancer progression & Treatment Resistance
Differential Gene Expression
Epigenetics & Proteomics
How can both loss and restoration of the accumulation of androgen receptor lead to treatment resistance?
The over express the HR to the point to where the drug is not functional, a gain of function mutations .
Hormone independent activation can also occur where the cancer cells can adapt and survive without the hormone.
Dr. Michael Q. Zhang
Functional relevance of enhancers
Pervasive Enhancer RNA (eRNA) transcription at active enhancers
Discovered in 2010 by Tae-Kyung Kim
Widespread transcription at neuronal activity-regulated enhancers
PAF1 is a pausing factor
PAF1 binds primarily to enhancers
Analysis of 4C-seq with SERPINE2 promoter
Heat Shock Genes are inducible
Read this review
Enhancer activity correlates with genes in heat shock response
Enhancer transcription affects Pol II pause release
Inducible enhancer and promoter pairs
The unexpected finding
The fate of an enhancer can be different from the promoter it regulates
Briefly describe what's genomic enhancer and Enhancer RNA (eRNA), and what their functions are.
An enhancer is a distal regulatory DNA segment that enhances the transcription of a target gene by interacting with the target gene promoter.
Enhancer RNA (eRNA) is a type of Non-coding RNA (ncRNA) transcribed from the enhancer that are tissue specific. Their function is thought to be in aiding in pulling Transcription Factor (TF) like beads on a string.
Dr. Duane Winkler
What role(s) can biochemists, who mostly work in vitro and at the molecular level, have in the mission to promote human health?
By creating a better understanding of molecules that play an important role in various diseases, such as Sod1 and ALS. A better understanding of all of the disease causing variants allows for better a better understanding of how to solve the issues with the protein
Dr. Faurck Morcos
Evolutionary Information Lab
Specificity & Design
Mutations throughout history provide examples on structure conservation
Can you take a sequence and get the folded protein
Direct Coupling Analysis predicts 3D contacts in proteins
Recent Research Efforts
DCA + Cross-links leads to better structure prediction
Protein-RNA specificity can be determined with Global probability models
DCA-MOL a visualization and analysis tool for evolutionary couplings
Modular swapping strategy
Evironmental sensing module(ESM)
DNA regognition module(DRM)
Inducibility of hybrid repressors
The compatibility score C(s) is a good predictor of repressor induction
Why is coevolutionary information a promising tool for protein design?
The proteins that evolved in parallel may have different sequences, but they can be used to better understand the relationship between changes and structure.
Dr. Tae Hoon Kim
Searching for meaning in the noncoding genome
A continuous time course genomic data can yield dynamic activity map to identify correct enhancer-promoter sets
How many enhancers in the human genome associated with all 20000 genes?
> 2 Million
Nicole J. De Nisco
Joined 2 years ago
Is health urine sterile?
Oct. 21st Dr. Lawrence Reitzer
Bacteria grow very quickly in urine
Motitlity and virulence
Swimming Motility most studied
Many forms of surface motility
Is motility required for UTIs?
Mouse model says yes
Clinician says yes
Pathogenic bacteria are fast
No IS(insertion sequence) elements
No glucose control of flagella synthesis
RNA-seq Analysis: Search for other metabolic differences
arcA mutant has aerobic growth defect
UPEC metabolism is different
Based on motility requirements and RNA-seq
Novel pathways and regulators
Novel carbohydrate transport
Why does UTI occur and recur?
Motility, metabolism of UPEC strains(bacterial factor), Urine composition(host factor) is why they occur.The infection becomes increasingly antibiotic resistant is why they recur.
2020-10-28 - Zhenyu Xuan
Computational Study of Genomic and Transcriptomic Changes Associated with Complex Diseases
Typical GWAS results
How could genomic variants cause disease?
Variants, Expression and Disease
Central Dogma -> phenotype
Some projects in my lab
Idenfity differential expressed genes expecially lncRNA
Study enhancer functions associated with gene expression and cell differentiation
Brg1 function in neuron activity and medulloblastoma
CTCF binding in chromatin structure regulation
Understand the non-coding regulators in embryo development
How could we connect genomic variants with potentially affected gene's function through computational methods?
Use GWAS to understand how the variants relate to the genes. Then we need to find the differential gene expression that relates to the disease using eQTLs, which helps to build up the GWAS edge.
Heme and Common Diseases
Heme and Lung Cancer
Heme-targeting agents effectively supress lung tumors
Heme-targeting agents effectively increase vascular oxygen saturation, normalize vascular function, and alleviate tumor hypoxia
Mentored Prof. Xuan
What are the two diseases related to heme being discussed today by Dr. Zhang?
Lung Cancer and Alzheimer's disease
Dr. Kelli Palmer
Natural colonizer of the gut
Briefly describe the native function of CRISPR-Cas systems in bacteria.
It's function is to provide an immune system against viral infections. It functions by taking small snippets from the viral genome and storing them in the bacteria genome as a new spacer. These spacers are then used to created crRNA which are used in CAS as guide RNAs, and they then match up with foreign genetic material and cleave it to inactivate the foreign genetic material.
He's from Manchester
Interests are mainly in Microbiology
Write a one sentence description for each of three different roles that nitric oxide plays in biology.
NO dilates blood vessels which are smooth muscles in a process called vasodilation. NO is generated by WBC and plays a role in the innate immune system and it's response. NO can also be used to for bacterial respiration when they are deprived of oxygen in an anaerobic process