WorldCat Identities

Kobilka, Brian K.

Works: 10 works in 10 publications in 1 language and 16 library holdings
Roles: Thesis advisor
Classifications: AS911.N9, 001.44
Publication Timeline
Most widely held works by Brian K Kobilka
The Nobel prizes 2012 : formerly les prix Nobel by Nobelstiftelsen( Book )

1 edition published in 2013 in English and held by 5 WorldCat member libraries worldwide

NMR spectroscopy for structural and dynamic studies of the beta2-adrenergic receptor by Michael Paul Bokoch( )

1 edition published in 2010 in English and held by 2 WorldCat member libraries worldwide

G protein coupled receptors (GPCRs) are seven transmembrane proteins that are expressed in all eukaryotic cells and tissues. These receptors play key roles in human physiology and disease. The goal of my work is to understand the molecular detail of ligand recognition by GPCRs, and how this process leads to conformational changes that manifest as cellular signaling. Meeting this goal will advance our knowledge of membrane protein biology. It will also reveal structural targets and physicochemical logic to aid pharmaceutical design. The age of GPCR structural biology recently arrived with the first x-ray structures of rhodopsin and the beta2 adrenergic receptor (beta2AR). However, membrane proteins are constantly fluctuating entities. Dynamic behavior is intrinsic to their function. As such, static x-ray structures alone are inadequate. Herein, I develop biophysical techniques to study these dynamic receptors. Using NMR spectroscopy, I characterize conformational changes in the extracellular region of the beta2AR, a surface rich with potential for drug design. I also explore the signaling properties of monomeric GPCRs and conformational changes of other macromolecules using single-molecule fluorescence. While many questions about GPCRs remain, I hope this work is a small step towards understanding these important, fascinating, and beautiful molecules
Optical techniques for integrated control and recording of neural activity by Raag Dar Airan( )

1 edition published in 2010 in English and held by 2 WorldCat member libraries worldwide

A long-standing objective of psychiatry has been the ability to both control and record the activity of precisely-defined populations of brain cells on the millisecond timescale most relevant for neural computation. Recent advances bring that goal increasingly near by leveraging the genetically-precise techniques of molecular biology with the high-speed, multiplexed command afforded by optical technologies to introduce and utilize light-sensitive neural activity control integrated with fast neural circuit imaging. In this thesis, I present exemplars of these technological advances and demonstrate their utility in illuminating the neural circuit basis of behaviors relevant to understanding psychiatric disease. I first show how fast neural circuit imaging may be integrated with optical neural control tools to develop insight into the role of genetically, developmentally, or projection defined populations of brain cells in mediating circuit-level physiological changes. I then demonstrate computational methods to analyze the resultant imaging data and apply fast circuit imaging to delineate links between hippocampal physiology and behavior in an animal model of depression. Finally, I present the development of a novel class of optically-activated, genetically-targetable control tools that permit optical control of G-protein coupled intracellular signaling; and the use of these molecular devices to determine causal roles of neuromodulatory inputs in reward processing. The development of these and similar optical modalities further improves the precision of questions addressable by the neuroscientist, and potentially the extent of disease treatable by the clinician
Structure and function of the M2 and M3 muscarinic acetylcholine receptors by Andrew Curtis Kruse( )

1 edition published in 2014 in English and held by 1 WorldCat member library worldwide

G protein-coupled receptors (GPCRs) constitute the largest single family of transmembrane receptors in humans, and play important roles in the regulation of normal human physiology and the pathogenesis of disease. The muscarinic acetylcholine receptors are a subfamily of GPCRs, and mediate the parasympathetic effects of acetylcholine, in addition to playing critical roles in cognition, memory, and maintenance of metabolic homeostasis. The muscarinic receptors have long served as an important model system for understanding GPCR function in general. Moreover, muscarinic receptors are important targets in the treatment of disease, and are also responsible for many of the side effects of commonly used therapeutic drugs targeting other receptors. To better understand these important receptors, I employed X-ray crystallography to determine the structures of the M2 and M3 muscarinic receptors in inactive, antagonist-bound conformations. Next, I used these structures for computational ligand screening, leading to the identification of over a dozen new muscarinic ligands. Finally, I determined the structure of the M2 muscarinic receptor in an active conformation stabilized by an antibody fragment. Similarly, a second structure of the M2 receptor bound to a positive allosteric modulator was resolved, offering structural insights into the allosteric modulation of GPCRs by drug-like molecules. Taken together, this work provides a framework for the interpretation of the extensive and growing body of biological and pharmacological data regarding muscarinic receptor function, and lays a foundation for future studies of muscarinic receptor biology
Structure-based engineering of immunomodulatory agents for the treatment of cancer by Aaron Michael Ring( )

1 edition published in 2016 in English and held by 1 WorldCat member library worldwide

Immune-based therapies for cancer are powerful, lasting, and generally less toxic than most other cancer treatment paradigms. Consequently, the development of new immunotherapeutic agents and the study of the interplay between tumors and the immune system have emerged as central lines of research for this nascent field of medicine. Here, I describe my efforts to improve an existing cancer immunotherapy (Interleukin-2), to study an experimental immunotherapeutic agent (Interleukin-15), and to generate novel protein therapeutics against an emerging target of cancer immune evasion (CD47). These studies highlight a structure- and mechanism-based approach to protein engineering in the development of next-generation cancer immunotherapies
Vitamin E-based glycoside amphiphiles for membrane protein structural studies1( )

1 edition published in 2018 in English and held by 1 WorldCat member library worldwide

Structural and functional characterizations of mitochondrial calcium uniporter by Chao Fan( )

1 edition published in 2018 in English and held by 1 WorldCat member library worldwide

In this thesis, I mainly worked on the structural and functional characterization of a mitochondrial calcium channel named MCU. Mitochondrial calcium plays critical roles in a wide range of fundamental cellular processes, including controlling the rate of ATP production, regulating the initiation of cell death and shaping cytosolic calcium signaling. Since fifty years ago when it was first demonstrated that fully energized mitochondria can rapidly load up calcium ions (Ca2+), the machinery behind this process has been extensively explored. This uptake is mediated by a highly selective calcium channel called the mitochondrial calcium uniporter (MCU), which resides on the inner mitochondrial membrane. The molecular identity of the uniporter was only uncovered relatively recently. MCU bears no discernable sequence similarity to other known channels and represents a new class in ion channels with its unique selectivity and conductance properties. In this thesis, I used both X-ray crystallography and single-particle cryo-electron microscopy to determine the structures of MCU from two species containing all domains, and I established rapid and efficient functional characterization platforms in cells and in liposomes. Unexpectedly, the stoichiometry, overall architecture, and local structural details of the new structures differed markedly from the NMR cMCU structure. The physiological relevance of those structures was corroborated by the observation of a consistent architecture across species and chemical environments, and by the systematical functional assays. Structural and functional characterizations provided insights into Ca2+ coordination, selectivity, and permeation, establishing a framework for understanding the mechanism of MCU function
Generic models of human vascular disease by Victor J Dzau( )

in English and held by 1 WorldCat member library worldwide

Sensing conformational dynamics of single trapped proteins in solution by Samuel David Bockenhauer( )

1 edition published in 2013 in English and held by 1 WorldCat member library worldwide

Proteins are macromolecular nanomachines that perform a wide variety of essential functions in living organisms. Distinct types of proteins in the cell serve as molecular sensors and signalers, sunlight-harvesting antennas and transducers, molecular motors for transport and metabolic energy storage, and oxidizers and reducers of physiological metal ions, to name a few. To achieve these complex functions, proteins are not static building blocks, but instead adopt multiple conformations in distinct functional states. These functions are inherently dynamic, meaning that methods capable of resolving dynamic behavior are necessary to fully elucidate protein function. Many bulk fluorescence methods have been used to study proteins by averaging together the signals from many copies of the same protein. However, such methods fail to capture distributions in protein conformations (e.g. mixtures of active and inactive states) and unsynchronized dynamics among these conformations (e.g. transition rates from inactive to active states under various conditions). Single-molecule fluorescence spectroscopy of proteins, on the other hand, allows direct observation of distributions and dynamics by watching only one protein at a time. In particular, a special device known as the Anti-Brownian ELectrokinetic (ABEL) trap can hold single fluorescently labeled proteins in solution for several seconds of spectroscopic observation without surface attachment, encapsulation, or the use of large beads. The ABEL trap combines fluorescence-based position estimation obtained by scanning a laser spot with the application of electrokinetic feedback forces to counter the Brownian motion of single proteins, one at a time. In this Dissertation I will describe my use of the ABEL trap technique to study dynamics of a variety of biomolecules, with emphasis on two proteins: the [beta]2-adrenergic receptor ([beta]2AR), an essential cellular signaling protein, and the peridinin-chlorophyll-protein (PCP), a sunlight-harvesting pigment-protein complex found in algae. In [beta]2AR, I observed a shift in protein conformation and in time scales of protein dynamics upon binding of an activating drug. In PCP, I observed two distinct classes of conformational change, indicating light-induced conformational flexibility, which may play a physiological role. Ongoing projects include resolving conformational substeps in FoF1 ATP synthase and measuring electron transfer kinetics of the multicopper oxidase Fet3p
Artificial intelligence methods for molecular property prediction by Evan N Feinberg( )

1 edition published in 2018 in English and held by 1 WorldCat member library worldwide

Audience Level
Audience Level
  Kids General Special  
Audience level: 0.78 (from 0.67 for Generic mo ... to 0.88 for Vitamin E- ...)

Alternative Names
Braiens Kobilka

Brajan Kobilka

Brian K. Kobilka

Brian Kent Kobilka

Brian Kobilka Amerikaans biochemicus

Brian Kobilka biochimico statunitense

Brian Kobilka chimiste américain

Brian Kobilka medical scientist

Brian Kobilka US-amerikanischer Biochemiker und Nobelpreisträger

Брайан Кобилка

Браян Кабылка

Браян Кобилка

Кобилка, Брайан

בריאן קובילקה

برايان كابيلكا

برائن کوبلکا

برایان کبیلکا

بریان کوبلکا

ब्रायन कोबिका

ব্রায়ান কোবিল্কা

பிரையன் கோபிலுக்கா

브라이언 코빌카


布莱恩·科比尔卡 醫學家


English (10)