Richard K. Zimmer

Bio: Richard K. Zimmer is an academic researcher from University of California, Los Angeles. The author has contributed to research in topics: Sperm & Sperm chemotaxis. The author has an hindex of 25, co-authored 53 publications receiving 2597 citations. Previous affiliations of Richard K. Zimmer include University of Queensland & University of California.

Identification of a testicular odorant receptor mediating human sperm chemotaxis.

Abstract: Although it has been known for some time that olfactory receptors (ORs) reside in spermatozoa, the function of these ORs is unknown. Here, we identified, cloned, and functionally expressed a previously undescribed human testicular OR, hOR17-4. With the use of ratiofluorometric imaging, Ca2+ signals were induced by a small subset of applied chemical stimuli, establishing the molecular receptive fields for the recombinantly expressed receptor in human embryonic kidney (HEK) 293 cells and the native receptor in human spermatozoa. Bourgeonal was a powerful agonist for both recombinant and native receptor types, as well as a strong chemoattractant in subsequent behavioral bioassays. In contrast, undecanal was a potent OR antagonist to bourgeonal and related compounds. Taken together, these results indicate that hOR17-4 functions in human sperm chemotaxis and may be a critical component of the fertilization process.

Chemical signaling processes in the marine environment

Abstract: Understanding the mechanisms by which environmental chemical signals, chemical defenses, and other chemical agents mediate various life-history processes can lead to important insights about the forces driving the ecology and evolution of marine systems. For chemical signals released into the environment, establishing the principles that mediate chemical production and transport is critical for interpreting biological responses to these stimuli within appropriate natural, historical contexts. Recent technological advancements provide outstanding opportunities for new discoveries, thus allowing quantification of interactions between hydrodynamic, chemical, and biological factors at numerous spatial and temporal scales. Past work on chemically mediated processes involving organisms and their environment have emphasized habitat colonization by larvae and trophic relationships. Future research priorities should include these topics as well as courtship and mating, fertilization, competition, symbiosis, and mi...

Physical constraints on ecological processes: a field test of odor‐mediated foraging

Abstract: The physicochemical environment can strongly constrain the outcome of ecological interactions such as predation, mating, and competition. This is especially true of processes mediated by the sense of olfaction, because wind and water currents control the dispersal of odor signals and act as ancillary cues during odor plume following. In the field, we examined how variations in the physical and chemical properties of odor plumes would alter the foraging behavior of the blue crab Callinectes sapidus, a common predator/ scavenger in tidal marsh creeks in the southeastern United States. We video-recorded re- sponses of naturally foraging crabs to odor plumes of varying composition and odor release rate (characteristic of clams of differing size). During each trial we presented crabs with an experimental plume that was a mixture of fluorescein-dyed seawater and clam mantle fluid, oyster mantle fluid, or a suite of amino acids, and a control plume which consisted of dyed seawater only. In addition to manipulating the chemical composition and odor release rate of the plume, we allowed flow speed to vary naturally with the tide. We tested for effects of odor composition, odor release rate, and flow speed on the success (i.e., finding the target) and efficiency (i.e., search path direction) of blue crab foraging. Mantle fluid solutions and wounded prey items elicited active search and upstream walking, while control and amino acid solutions had no effect on crab behavior. Odors released at a low rate (either low volume flow or low concentration) elicited fewer responses from crabs, and the resulting search was less efficient and less successful than responses to odors released at higher rates. Ambient current speed also affected both search success and efficiency. There was a decline in search success when current speed in the tidal channel was below 1 cm/s; search success remained constantly high, however, when current speed was above this threshold. Search efficiency was directly proportional to ambient current speeds. Such relationships between hydrodynamic and chemical properties of the environ- ment and foraging success and efficiency suggest that variation in the physicochemical environment can influence the detectability of prey and strategies employed by foragers. These results extend beyond the foraging of marine crustaceans into other olfactory- mediated interactions and habitats.

Sex and flow: the consequences of fluid shear for sperm-egg interactions.

Abstract: SUMMARY Fertilization is a complex interaction among biological traits of gametes and physical properties of the fluid environment. At the scale of fertilization (0.01–1 mm), sperm encounter eggs while being transported within a laminar (or viscous) shear flow. Varying laminar-shear in a Taylor-Couette flow tank, our experiments simulated important aspects of small-scale turbulence within the natural habitats of red abalone ( Haliotis rufescens ), a large marine mollusk and external fertilizer. Behavioral interactions between individual cells, sperm–egg encounter rates, and fertilization success were quantified, simultaneously, using a custom-built infrared laser and computer-assisted video imaging system. Relative to still water, sperm swam faster and moved towards an egg surface, but only in comparatively slow flows. Encounter rate, swim speed and orientation, and fertilization success each peaked at the lowest shear tested (0.1 s –1 ), and then decayed as shear increased beyond 1.0 s –1 . The decay did not result, however, from damage to either sperm or eggs. Analytical and numerical models were used to estimate the propulsive force generated by sperm swimming ( F swim ) and the shear force produced by fluid motion within the vicinity of a rotating egg ( F shear ). To first order, male gametes were modeled as prolate spheroids. The ratio F swim / F shear was useful in explaining sperm–egg interactions. At low shears where F swim / F shear >1, sperm swam towards eggs, encounter rates were pronounced, and fertilization success was very high; behavior overpowered fluid motion. In contrast, sperm swimming, encounter rate and fertilization success all decayed rapidly when F swim / F shear <1; fluid motion dominated behavior. The shears maximizing fertilization success in the lab typically characterized natural flow microenvironments of spawning red abalone. Gamete behavior thus emerges as a critical determinant of sexual reproduction in the turbulent sea.

Structural diversity of G protein-coupled receptors and significance for drug discovery

Abstract: G protein-coupled receptors (GPCRs) are the largest family of membrane-bound receptors and also the targets of many drugs. Understanding of the functional significance of the wide structural diversity of GPCRs has been aided considerably in recent years by the sequencing of the human genome and by structural studies, and has important implications for the future therapeutic potential of targeting this receptor family. This article aims to provide a comprehensive overview of the five main human GPCR families--Rhodopsin, Secretin, Adhesion, Glutamate and Frizzled/Taste2--with a focus on gene repertoire, general ligand preference, common and unique structural features, and the potential for future drug discovery.

Sperm transport in the female reproductive tract

Abstract: At coitus, human sperm are deposited into the anterior vagina, where, to avoid vaginal acid and immune responses, they quickly contact cervical mucus and enter the cervix. Cervical mucus filters out sperm with poor morphology and motility and as such only a minority of ejaculated sperm actually enter the cervix. In the uterus, muscular contractions may enhance passage of sperm through the uterine cavity. A few thousand sperm swim through the uterotubal junctions to reach the Fallopian tubes (uterine tubes, oviducts) where sperm are stored in a reservoir, or at least maintained in a fertile state, by interacting with endosalpingeal (oviductal) epithelium. As the time of ovulation approaches, sperm become capacitated and hyperactivated, which enables them to proceed towards the tubal ampulla. Sperm may be guided to the oocyte by a combination of thermotaxis and chemotaxis. Motility hyperactivation assists sperm in penetrating mucus in the tubes and the cumulus oophorus and zona pellucida of the oocyte, so that they may finally fuse with the oocyte plasma membrane. Knowledge of the biology of sperm transport can inspire improvements in artificial insemination, IVF, the diagnosis of infertility and the development of contraceptives.

Diverse Applications of Nanomedicine

Abstract: The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic.

Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation

Abstract: Olfactory receptors are G protein-coupled receptors that mediate olfactory chemosensation and serve as chemosensors in other tissues. We find that Olfr78, an olfactory receptor expressed in the kidney, responds to short chain fatty acids (SCFAs). Olfr78 is expressed in the renal juxtaglomerular apparatus, where it mediates renin secretion in response to SCFAs. In addition, both Olfr78 and G protein-coupled receptor 41 (Gpr41), another SCFA receptor, are expressed in smooth muscle cells of small resistance vessels. Propionate, a SCFA shown to induce vasodilation ex vivo, produces an acute hypotensive response in wild-type mice. This effect is differentially modulated by disruption of Olfr78 and Gpr41 expression. SCFAs are end products of fermentation by the gut microbiota and are absorbed into the circulation. Antibiotic treatment reduces the biomass of the gut microbiota and elevates blood pressure in Olfr78 knockout mice. We conclude that SCFAs produced by the gut microbiota modulate blood pressure via Olfr78 and Gpr41.

The biology of infertility: research advances and clinical challenges

Abstract: Reproduction is required for the survival of all mammalian species, and thousands of essential 'sex' genes are conserved through evolution. Basic research helps to define these genes and the mechanisms responsible for the development, function and regulation of the male and female reproductive systems. However, many infertile couples continue to be labeled with the diagnosis of idiopathic infertility or given descriptive diagnoses that do not provide a cause for their defect. For other individuals with a known etiology, effective cures are lacking, although their infertility is often bypassed with assisted reproductive technologies (ART), some accompanied by safety or ethical concerns. Certainly, progress in the field of reproduction has been realized in the twenty-first century with advances in the understanding of the regulation of fertility, with the production of over 400 mutant mouse models with a reproductive phenotype and with the promise of regenerative gonadal stem cells. Indeed, the past six years have witnessed a virtual explosion in the identification of gene mutations or polymorphisms that cause or are linked to human infertility. Translation of these findings to the clinic remains slow, however, as do new methods to diagnose and treat infertile couples. Additionally, new approaches to contraception remain elusive. Nevertheless, the basic and clinical advances in the understanding of the molecular controls of reproduction are impressive and will ultimately improve patient care.