Showing posts with label UPC. Show all posts
Showing posts with label UPC. Show all posts

Monday, March 9, 2020

MCB Colloquium | Dr. Yang Yang

   Yang Yang Flyer by uscbiscgrad on Scribd

MEB Seminar | Dr. Nicole Ratib

Dr. Nicole Ratib
Post-Doc, USC, MEB (PI: Dr. Cameron Thrash)
Research Profile

Genomic and physiological characterization of Escherichia coli evolving in long-term batch culture

Tuesday, March 10, 12 PM, AHF 153 (Torrey Webb Room)

Abstract: In most natural environments, bacteria spend much of their time under conditions of starvation and stress. Long-term batch cultures are an excellent laboratory system to study adaptation during nutrient stress because cells are incubated for relatively long periods of time, months to years, without the addition of nutrients. During long-term batch culture cells adapt to acquire energy from cellular detritus creating a complex and dynamic environment for mutants of increased relative fitness to exploit. To characterize the population dynamics and identify beneficial alleles, we analyzed the genomes of 1117 clones isolated from a single long-term batch culture inoculated with a single clone and incubated for 1200 days. A total of 679 mutations were identified including single nucleotide polymorphisms, indels, movement of mobile genetic elements, large deletions up to 64kbp and amplifications up to ~500kbp. During the 3.3-year incubation, two main lineages diverge and continuously evolve. There is evidence of at least two instances of a fixed mutation reverting back to the wild type allele, suggesting beneficial mutations may later become maladaptive. Most of the mutated genes encode proteins involved in metabolism, transport, or transcriptional regulation. Clones from the two lineages are physiologically distinct based on outgrowth in fresh medium and competition against the parental strain. Similar population dynamics and mutated genes were detected in three parallel populations sequenced through day 60 providing evidence for positive selection. These data provide new insight into the population structure and mutations that may be beneficial during periods of starvation in evolving bacterial communities.

Monday, March 2, 2020

QCB Faculty Candidate Seminar | Dr. Geoffrey Fudenberg

Dr. Geoffrey Fudenberg
Bioinformatics Fellow, UCSF, Gladstone Institute
Research Profile

Genomes in 3D: connecting structure and function

Thursday, March 5, 2 PM, RRI 101

Abstract: How are micron-long chromosomes spatially organized by molecular interactions between proteins at the nanometer scale? Acting as a molecular microscope, genome-wide chromosome conformation capture (Hi-C) reveals that genomes are intricately folded in 3D. Here I describe how biophysical simulations and machine learning approaches enable interpretation of these large-scale genomic datasets. First, I describe converging theoretical and experimental evidence arguing that Cohesin-mediated loop extrusion with CTCF-defined barriers plays a crucial role in interphase. Second, I describe how convolutional neural networks enable accurate predictions of genome folding from DNA sequence alone. Together, these advance our understanding of the proteins driving and the sequences underpinning 3D genome folding.

Sunday, February 23, 2020

QCB Faculty Candidate Seminar | Dr. Assaf Amitai

Dr. Assaf Amitai
Post-Doctoral Researcher, MIT
Research Website

Geometry and stochastic dynamics in biological systems

Thursday, February 27, 2 PM, RRI 101

Abstract: The interaction of proteins with chromatin regulates many cellular functions. Most DNA-binding proteins interact both non-specifically and transiently with many chromatin sites, as well as specifically and more stably with cognate binding sites. These interactions and chromatin structure are important in governing protein dynamics. By analyzing the motion of CTCF, a DNA binding protein responsible for chromosomal organization, we inferred that it interacts with a new type of small nuclear domains. These domains, composed of RNA, are central in guiding CTCF to find its cognate binding site. Hence, weak transient interactions govern chromatin organization and dynamics. In the second part of the talk, I will describe recent advances in the development of a universal vaccine for the influenza virus. Using coarse-grained molecular dynamics simulations and a population scale models of the adaptive immune system, we study the immune response to nanoparticles presenting flu proteins at unique geometries and compositions. We show that these nanoparticles can direct the immune response in distinct evolutionary paths, and elicit the creation of antibodies of high breadth - capable of neutralizing multiple flu strains.

MCB Colloquium | Dr. Cornelius Gati

   Gati Flyer by uscbiscgrad on Scribd

MCB Colloquium | Dr. Xinghong Dai

   Xinghong Dai Flyer by uscbiscgrad on Scribd

Monday, February 17, 2020

QCB Faculty Candidate Seminar | Dr. David Zeevi

Dr. David Zeevi
Independent Fellow, Rockerfeller University, Center for Studies in Physics & Biology
Research Website

Mining the marine microbiome for remediation targets: lessons from the human microbiome

Thursday, February 20, 2 PM, RRI 101

Abstract: Microbial communities can have an immense effect on their environment and are strongly affected by it. Using new methods for metagenomic sequencing analysis, we systematically identified microbial genomic structural variants and found them to be highly prevalent in the gut microbiome and to correlate with disease risk factors (Zeevi et al., Nature 2019). Our results suggest that these variants facilitate adaptation to environmental stress. Exploring genes that are clustered in the same variant, we uncovered potential mechanistic links between microbiome and its host. Inspired by our discovery of potential microbial adaptation to host pressures, I developed a strategy for mining marine microbiome samples for novel bioremediation genes. To this end, we devised a high-throughput evolutionary analysis, and revealed an unexpected insight into the structure of our genetic code (Shenhav and Zeevi, bioRxiv 2019). Our primary analyses uncovered overwhelmingly strong purifying selective pressure across marine microbial life. This selection was highly correlated with nutrient concentrations and has led us to explore robustness in the genetic code, common to nearly all life forms. We show that the structure of the genetic code, along with amino acid choices across all kingdoms of Life, confers robustness to mutations that incorporate additional nitrogen and carbon into protein sequences. By accounting for this nutrient-conservation-driven purifying selection, we will be able to expose a new layer of selection associated with marine pollution.

MCB Colloquium | Dr. Xianrui Cheng

   Xianrui Cheng Flyer by uscbiscgrad on Scribd

Sunday, February 2, 2020

MCB Colloquium | Dr. Joseph Nadeau

MEB Seminar | Dr. Leslie Babonis

Dr. Leslie Babonis
Research Assistant Scientist, University of Florida, Whitney Lab for Marine Bioscience
Research Profile

Understanding biodiversity, one cell at a time

Thursday, February 6, 12 PM, AHF 153 (Torrey Webb Room)

Abstract: I study novelty. Specifically, I am interested in understanding the factors that drive the origin and diversification of novel cell types. More than just taxon-specific oddities, novel cell types can promote niche specialization and facilitate speciation events; thus, studying novelty is critical for understanding the evolution of biodiversity. One of my favorite projects focuses on understanding the mechanisms driving morphological and functional specialization of cnidocytes (stinging cells) across cnidarians (corals, jellyfish, and their kin). Using a combination of observational and functional techniques, I have constructed a cnidocyte gene regulatory network that I use to test hypotheses about the evolutionary origin of this truly bizarre lineage of cells. Surprisingly, the fate of this novel cell lineage seems to have been acquired through recycling and reorganization of an old gene regulatory network, rather that the origin of a novel regulation strategy.

MCB Colloquium | Dr. Jake Harris

   Harris Flyer Flyer by uscbiscgrad on Scribd

Monday, January 27, 2020

MEB Seminar | Dr. Allie Graham

Dr. Allie Graham
NSF PRFB Fellow, Oregon State University
Research Website

From the Mountains to the Sea: Comparative Genomics of Mechanisms Underlying the Physiological Response to Low Oxygen

Tuesday, January 28, 12 PM, AHF 153 (Torrey Webb Room)

Abstract: Environmental variables can exert a considerable selective pressure across the entire organism – from their genome to their physiology. Organisms living in extreme environmental conditions provide excellent systems to investigate numerous basic questions about the limits of an organism's ability to adapt, to understanding the inherent repeatability of molecular adaptation, and thus the origins of biodiversity, by examining both phenotypic and genotypic novelty. My work uses both integrative and comparative approaches to understand the mechanisms underpinning the response to such environmental variables, with a focus on oxygen availability (i.e. hypoxia). This talk will journey through my previous work on high-altitude adaptation in Andean duck species, to my current work on hypoxia in copepods (and other crustaceans), and conclude with how my discoveries opened up numerous exciting avenues for future work in aquatic invertebrates.

MCB Colloquium | Dr. Bushra Raj

   Bushra Raj Flyer by uscbiscgrad on Scribd

Tuesday, January 21, 2020

Marine & Environmental Biology Seminar | Dr. Phillip Cleves

Dr. Phillip Cleves
Post-Doctoral Research Fellow, Stanford University
Research Profile |

Molecular and cellular bases of cnidarian-dinoflagellate symbiosis and its breakdown

Tuesday, January 21, 12 PM, AHF 153 (Torrey Webb Room)

Abstract: The symbiosis between corals and dinoflagellate algae is essential to the energetic requirements of coral-reef ecosystems. However, coral reefs are in danger due to elevated ocean temperatures and other stresses that lead to the breakdown of this symbiosis and coral "bleaching". Despite the importance of coral reefs, the molecular basis of how corals maintain a healthy symbiosis and avoid bleaching is poorly understood, in part because of the lack of a tractable genetic model system. The small anemone Aiptasia is symbiotic with algal strains like those in reef-building corals but has many experimental advantages, making it an attractive laboratory model for cnidarian symbiosis.  To explore the transcriptional basis of heat-induced bleaching, we used RNAseq to identify genes that are differentially expressed during a time course of heat stress of symbiotic and aposymbiotic Aiptasia strains. We observed a strong upregulation of hundreds of genes at times long before bleaching begins in symbiotic anemones. The putative promoters of these early stress-response genes are enriched for binding sites for the NFB and HSF1 transcription factors, suggesting that many of these genes share core transcriptional control. The overall expression patterns were similar between the symbiotic and aposymbiotic anemones, indicating that many of the expression changes are not specific to the presence of the algae. Nonetheless, reducing HSF1 activity with a pharmacological inhibitor resulted in more severe bleaching, suggesting that this symbiont-independent stress response is protective against bleaching.
           
Genetic tools are needed to allow rigorous functional testing of the roles of candidate genes in symbiosis and bleaching. Recently, we have developed methods for knocking down and overexpressing genes of interest in Aiptasia. Meanwhile, we have successfully used the CRISPR/Cas9 technology to create genetic changes in embryos of the coral Acropora millepora. We used this technology to knock out HSF1 and demonstrated its role in coral heat tolerance. Through the establishment of both gain-of-function and loss-of-function methods in both Aiptasia and corals, it will be possible to exploit the year-round spawning of Aiptasia to perform initial tests of gene function in cnidarian-algal symbiosis and then further test the discoveries made using similar technologies in corals.


Molecular & Computational Biology Colloquium | Dr. Jacob Musser

Dr. Jacob Musser
Post-Doctoral Fellow, EMBL, Developmental Biology Unit (Heidelberg)
Research Profile | Abstract

Few cell types, many functions: The evolutionary origin of division of labor among animal cells

Thursday, January 23, 10:30-11:45 AM, RRI 101

Abstract: Sponges are the sister group to nearly all other animals, and lack a nervous system, musculature, and gut. However, genes encoding important neuronal proteins, including key synaptic proteins, have been found in sponge genomes. Using single-cell RNAseq, single-molecule FISH, and Focused Ion Beam SEM (FIB-SEM) we generate a comprehensive molecular and morphological characterization of cell types in Spongilla lacustris, a freshwater demosponge. We identify many specialized cell types bearing functional and regulatory signatures similar to those of other animals. This includes contractile epithelial cells, which we demonstrate experimentally are responsive to nitric oxide signaling, phagocytes involved in innate immunity, and digestive cells that express a nearly complete set of postsynaptic genes. Remarkably, we also find immune cells expressing presynaptic genes and show via FIB-SEM that they send long projections that directly contact and enwrap microvilli of 'postsynaptic' digestive cells. This reveals new evidence linking neuronal and immune function in sponges, and suggests a primordial neuro-immune system cleared intruders and controlled ciliary beating for feeding.

Quantitative & Computational Biology Faculty Candidate Seminar | Yang Yang

Yang Yang
Ph.D. Candidate, Carnegie Mellon University, Computational Biology
Research Website

Computational Methods for Multi-Species Comparison of 3D Genome Structure and Function

Thursday, January 23, 2 PM, RRI 101

Abstract: Recent development in chromatin interaction mapping technologies have greatly advanced the study of three-dimensional (3D) genome organization, which is closely related to vital genome functions such as DNA replication timing (RT) and transcription. However, the principles underlying 3D genome organization and the detailed patterns on how the 3D genome has changed in mammalian evolution remain largely unclear. In this talk, I will primarily introduce two probabilistic models that I have developed during my Ph.D. research: Phylo-HMGP and Phylo-HMRF, which provide the new generic frameworks for genome-wide comparison of continuous genomic features, including RT and Hi-C data for 3D genome structures. The methods incorporate the temporal dependencies of species in the context of evolution with the spatial dependencies of genomic loci, to identify genome-wide evolutionary patterns of continuous genomic features. Real data applications to the RT data and Hi-C data from multiple primate species demonstrated the effectiveness of the models and offered high resolution characterization of evolutionary patterns of 3D genome structure and function. Together, the methods have the potential to help reveal genomic regions with conserved or species-specific structural and regulatory roles, and provide key insights into nuclear organization and function through cross-species comparisons.

Monday, January 13, 2020

QCB Colloquium | Dr. Serghei Mangul

Dr. Serghei Mangul
Assistant Professor, USC School of Pharmacy
Lab Website

Dumpster diving in RNA-sequencing to study the immune receptor repertoires and microbial communities

Thursday, January 16, 2 PM, RRI 101

Abstract: Assay-based approaches provide a detailed view of the adaptive immune system by profiling T- and B-cell receptor (TCR/BCR) repertoires. However, these methods are costly, time-consuming, and lack the scale of RNA sequencing (RNA-seq). The seminar will introduce bioinformatic methods that mine discarded sequences and produce rich research level data including T and B cell receptor sequences, microbiome, genome-wide germline genotypes, and rDNA and mtDNA copy number.  We have applied our methods to GTEx multi-tissue RNA-Seq data (n=8,555) and Profile OncoPanel cancer sequencing data (n=20,000). We validated the accuracy of our methods and showed their utility through replication of known genetic associations. The presented systematic atlas of immunological sequences data contains one of the largest collections of immune receptor sequencing across a broad range of tissue. Additionally, we investigated the functional mechanisms underlying connections between the immune system, microbiome, and disease.

Monday, December 2, 2019

MEB Seminar | Dr. Casey Mueller

Dr. Casey Mueller
Assistant Professor, CSUSM, Biology
Lab Website

Thermal physiology: exploring themes of development and variability in different animal models

Tuesday, Dec. 3, 12 PM, AHF 153 (Torrey Webb Room)

Abstract: Dr. Mueller will present some of her lab’s data on copepods, as well as some work on chorus frogs and possibly rainbow trout.  Many of the ideas can be applied to marine organisms.