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Aging and Neurodegeneration

• Needhi Bhalla, (MCD) Chromosome Structure and Function during Meiosis
• Lindsay Hinck (MCD) Loss of Growth Control and Cancer
• Glenn Millhauser (Chem) Remarkable Protein Structures... and Where They Go Wrong in Disease
• Jevgenij Raskatov (Chem) Disease-Oriented Chemical Biology
• Jeremy Sanford (MCD) Post Transcriptional Control of Gene Expression
• Bill Saxton (MCD) Organelle Transport and Neurodegeneration
• Nik Sgourakis (Chem) Modelling the Structures of Protein Complexes from Sparse Experimental Data
• Don Smith (METX) Molecular and Functional impacts of Neurotoxic Agents
• Michael Stone (Chem) Assembly, Structure, and Regulation of the Telomerase Ribonucleoprotein
• Susan Strome (MCD) Regulation of Germ Cell Development in C. elegans
• Yi Zuo (MCD) Synapse Plasticity and Learning/Memory

Prof. Needhi Bhalla Chromosome Structure and Function during Meiosis

Needhi Bhalla, Dept. of MCD Biology

The Bhalla lab isinterested in the mechanisms that ensure that chromosomes segregate correctly during cell division, particularly in meiosis. During this specialized cell division, diploid cells give rise to haploid gametes, such as sperm and eggs, so that diploidy is restored by fertilization. Defects in meiosis can generate gametes, and therefore embryos, with the incorrect number of chromsomes. These aberrations in chromosome number, also referred to as aneuploidy, typically produce inviable embryos. It is estimated that 30% of human miscarriages are due to aneuploidy. In some cases, the presence of an extra copy of a chromosome can be tolerated by a human embryo but results in serious developmental disorders, such as Down and Klinefelters syndrome. [More]

Bhalla Publications
Needhi Bhalla's Email

Prof Lindsay HInckLoss of Growth Control and Cancer

Lindsay Hinck, MCD Biology

One in eight women in the United States will develop breast cancer in her lifetime. Only about 15% of these cancers have been linked to specific gene mutations; therefore a major challenge in breast cancer research is to identify the causes of the disease. We have identified Slits as breast tumor suppressors that regulate several critical pathways controlling cell proliferation and migration. Current research focuses on developing therapeutic strategies to target these pathways. [More]

Hinck Publications Lindsay Hinck's Email

Prof MillhauserRemarkable Protein Structures... and Where They Go Wrong in Disease

Glenn Millhauser, Dept. of Chemistry and Biochemistry

In modern biochemistry, structural determination is essential for understanding the function of biomolecules. Scientists in Glenn Millhauser's laboratory use peptide synthesis, nuclear magnetic resonance spectroscopy (NMR), and electron paramagnetic spin resonance spectroscopy (EPR) to examine the structure and analyze the function of proteins that have been implicated in several debilitating diseases. This includes the prion protein, which is responsible for mad cow disease and the related human affliction, Creutzfeldt-Jakob disease. They have also examined a novel signaling molecule, called AGRP, which is involved in energy balance and metabolic pathologies, such as diabetes and obesity. [More]
Millhauser Publications Glenn Millhauser's E-Mail

Prof. Jevgenij A. RaskatovDisease-Oriented Chemical Biology

Jevgenij A. Raskatov, Dept. of Chemistry and Biochemistry

Raskatov draws inspiration from aging-related medicinally challenging questions, which are becoming increasingly pressing as life expectancy continues to rise (the cancer/inflammation interface is of specific interest). Raskatov's lab identifies biomolecular signaling nodes that are sufficiently well-understood at the molecular level, so that a biology problem can be translated into a chemistry problem. As chemists, their goal is to synthesize molecules and study their properties by means of NMR spectroscopy (1), crystallography (2) and DFT computation (3). Molecular scaffolds that show initial promise are tested in relevant biological systems both in cell culture (4) and in vivo (5). [More]

Jevgenij Raskatov's Publications Jevgenij Raskatov's Email

Prof. Jeremy SanfordPost Transcriptional Control of Gene Expression

Jeremy Sanford , Dept. of MCD Biology

Accumulation of somatic mutations during our life history contributes to the stochastic nature of aging and plays a key role in the onset of disease. The focus of this project is to understand how mutations induce disease phenotypes, a question directly relevant to many aspects of aging research. Here we investigate the hypothesis that disease-causative point mutations induce aberrant processing of messenger RNA by disrupting the specificity of protein-RNA interactions. Our first step towards elucidating the impact of disease-causing mutations will be to map sites of RNA-protein interactions occurring in the context of living cells. These comprehensive maps will be leveraged to identify disease-causing mutations with the potential to abolish or create protein-binding sites within RNA transcripts. Our computational predictions of toxic RNA elements will be validated in the laboratory using patient-derived cell lines to assay RNA processing of the endogenous disease-gene. Our work in this area promises to improve our understanding of the basic mechanisms governing gene expression and will directly translate to improved diagnosis and treatment of aging related diseases. [More]

Jeremy Sanford's Publications Jeremy Sanford's Email

Prof Bill SaxtonOrganelle Transport and Neurodegeneration

Bill Saxton, Dept. MCD Biology

The Saxton lab studies mechanisms that drive intracellular transport and cytoplasmic organization, using Drosophila as a model organism. To generate and maintain proper cytoplasmic order and thus their complex functions, cells use microtubules and force-generating motor proteins to transport RNAs, proteins, mitochondria and other organelles to appropriate locations. Neurons are especially dependent on such microtubule-based cytoplasmic transport, because their signaling functions rely on extraordinarily long cytoplasmic extensions (axons and dendrites) that require import of many components from their cell bodies ... [More]

Saxton Publications Bill Saxton's Email

Prof Nik SgourakisModelling the Structures of Protein Complexes from Sparse Experimental Data

Nik Sgourakis, Dept. of Chemistry and Biochemistry

Research in the Sgourakis lab focuses on elucidating the structures of important protein complexes involved in Immune recognition of viruses, bacterial secretion and neurodegeneration. Determining the structural basis of protein-protein interactions and self-assembly will help clarify fundamental biological mechanisms and facilitate the design of novel therapeutics. To achieve this, structure-based modelling at sufficient resolution is required. The Sgourakis lab is developing and implementing new tools based on Nuclear Magnetic Resonance spectroscopy and complementary sources of experimental data alongside advanced computational sampling methods. The integration of a range of experimental and computational approaches enables structural studies of proteins and their complexes at high resolution. [More]
Sgourakis Publications Nik Sgourakis' Email

Prof Don Smith Molecular and Functional impacts of Neurotoxic Agents

Don Smith, Microbiology and Environmental Toxicology

It is becoming clear that exposures to environmental toxins, such as lead, mercury, and arsenic can cause or contribute to the development of diseases in humans. For example, some neurobehavioral and neurodegenerative disorders, such as learning deficits and Parkinsonism have been linked to elevated lead and manganese exposures in children and manganese exposures in adults, respectively. The Smith lab explores basic mechanisms underlying how toxic metal exposures contributes to cellular effects and disease. [More]

Smith Publications Don Smith's Email

Prof Michael StoneAssembly, Structure, and Regulation of the Telomerase Ribonucleoprotein

Michael Stone, Dept. of Chemistry and Biochemistry

The Stone Research Group combines the use of biochemical and structural methods with newly emerging single-molecule techniques to probe the dynamics of protein-nucleic acid interactions and the molecular mechanisms of biological motors.  Our current area of focus is the structure and function of the telomerase ribonucleoprotein, an RNA-dependent DNA polymerase that maintains genomic stability by synthesizing repetitive DNA sequences at chromosome termini.  These short DNA repeats provide the foundation for specialized chromatin structures, called telomeres, which prevent deleterious chromosome fusion events by differentiating chromosome ends from sites of DNA damage.  It has been shown that telomere length typically decreases with every round of cell division, leading to the so-called ‘molecular clock’ hypothesis, wherein telomere length serves as a signal to control cellular lifespan. This notion is consistent with the finding that active telomere DNA synthesis is normally restricted to rapidly dividing cell types such as stem cells and the majority of human cancers. Our research seeks to elucidate physical mechanisms governing telomere length regulation, and in turn establish a conceptual framework within which to develop novel diagnostic and therapeutic strategies for human disease. [More]

Stone Publications Michael Stone's Email

Prof Susan StromeRegulation of Germ Cell Development in C. elegans

Professor Susan Strome, MCD Biology

Germ cells (the cells that give rise to eggs and sperm) have special properties. Their immortality allows them to be perpetuated from generation to generation, and their totipotency allows them to generate all of the diverse cell types of the body in each generation. Our lab investigates the molecular mechanisms used by germ cells to establish and maintain their identity, immortality, and totipotency. We study germ cells in the model organism C. elegans using a wide variety of approaches, including genetics, imaging, molecular biology, biochemistry, and whole-genome microarray and sequencing technologies. Our current focus areas are transmission of chromatin states and control of gene expression in germ cells, and regulation of RNA metabolism by germline-specific cytoplasmic "P granules". [More]

Strome Publications Susan Strome's E-Mail

Prof Yi ZuoSynapse Plasticity and Learning/Memory

Yi Zuo, Dept. of MCD Biology

The human brain is an extremely complicated organ, in which billions of neurons make trillions of connections. Synapses are the principal sites at which neurons communicate with one another. Experience-dependent modification of synaptic structure and function provides a cellular mechanism for learning and memory, while abnormal synaptic connections are hallmarks of many neurological and psychiatric disorders. My laboratory studies how the neuronal circuitry is rewired during learning and memory formation, and investigates the cellular mechanisms underlying structural changes of synapses under both physiological and pathological conditions. ( [More]
Zuo Publications Yi Zuo's E-Mail

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