2018 Pilot Project Awards – UC Irvine Microbiome Initiative

Check out our Pilot Project Proposal page for selection criteria and award details.

The microbiome in KCNE2-linked heart failure
Geoffrey W. Abbott
Dept. of Physiology & Biophysics, School of Medicine

Project Summary

Heart failure (HF) affects 40 million people worldwide, causing 50% mortality within 5 years of diagnosis. We recently discovered that the KCNE2 potassium channel regulatory subunit is linked to HF. KCNE2 is required for gastric acid secretion, but is also important for heart rhythm and contractility. Global Kcne2 gene deletion in mice causes achlorhydria (loss of gastric acid secretion) and several factors predisposing to HF (e.g., diabetes, atherosclerosis), and causes terminal HF at 12-15 months. Paradoxically, cardiac- specific Kcne2 deletion causes terminal HF much earlier, at 6 months. Thus, an unknown factor linked to global Kcne2 deletion is highly effective at delaying HF. We also recently found we can delay HF in cardiac-specific Kcne2 knockout mice using omeprazole to prevent gastric acid secretion. In this pilot project, we aim to elucidate if alterations in the gut microbiome might contribute to the cardioprotective effects of global Kcne2 deletion and/or omeprazole-induced achlorhydria.

Influence of Renal Cancer on the Urogenital Microbiome
Taylor Capretz and Ralph V. Clayman
Dept. of Urology, School of Medicine

Project Summary

The role of the urinary microbiome on kidney cancer has not been studied to date. The primary aim of this pilot project is to observe potential differences in the urogenital microbiome of patients with kidney cancer and patients without kidney cancer. Our team will collect urine samples and tumor tissue samples from the kidney cancer group and urine samples from the control group. If there is an abundance of a specific bacterial genus found in the tumor tissue samples of kidney cancer patients, we will analyze the patient’s urine sample for the same bacterial genus.

If a difference is observed between patients with kidney cancer and patients without kidney cancer, this will add to our understanding of the relationship between the urogenital microbiome and kidney cancer. In addition, this study could provide preliminary data to aid the development of a microbiome-targeting diagnostic tool for kidney cancer.

Consequences of plant adaptation for the associated microbial community
Jordan Croy and Kailen Mooney
Dept. of Medicine, School of Medicine

Project Summary

Climate change will produce novel abiotic and biotic environments, posing a critical question for evolutionary ecologists in the 21^st century: how will ecological communities respond? We use Artemisia californica, a foundational shrub in the coastal sage scrub ecosystem, as a model system for studying how plants adapt to multiple stressors (e.g. drought and herbivory) in the environment, and the effects of this adaptation on their associated biotic communities. By growing plants sourced from different environments within a single environment (i.e. common garden), these gardens serve as a window into the plant’s genetics. We then measure plant traits and identify the associated arthropod and leaf microbial communities for each plant within the common garden. As a result, this work links genetic variation in plant traits to the associated food web, which will provide insight into how food webs might change under climate change as plants adapt to novel environments.

Evaluating the Microbiome in Myeloproliferative Neoplasm
Angela Fleischman
Dept. of Medicine, School of Medicine

Project Summary

The goal of this project is to determine whether people with myeloproliferative neoplasm (MPN), a chronic blood cancer with high levels of inflammation, have different types of bacteria in their gut than do people without MPN. An unbalanced profile of gut bacteria may promote chronic inflammation and drive the development and/or progression of MPN. If we find that MPN patients do indeed have an abnormal profile of gut bacteria then we will then move onto test therapies to restore the profile of gut bacteria back to normal in MPN patients.

Microbial diversity in the guts of wild abalone and pāua from across the Pacific
Alyssa R. Frederick and Donovan P. German
Dept. of Ecology and Evolutionary Biology, Charlie Dunlop School of Biological Sciences

Project Summary

Abalone are marine snails that live in rocky shores around the world, are important  ecological habitat engineers, and once supported a huge commercial fishery in California. After overfishing caused large declines in wild abalone stocks in California, withering syndrome (WS), a disease that leads to death, wiped out much of what was left. WS infects the digestive system of abalone, yet the understanding of healthy gut function in wild abalone is extremely limited. Enzyme function and the contribution of microbial communities to digestion are largely understudied, especially in wild animals. This project aims to fill this critical research gap by identifying the gut microbial communities and their function in two species of abalone, red abalone of California and pāua of New Zealand. Pāua have never been exposed to WS, so they provide a perfect natural control for examining microbial communities in healthy and infected wild abalone.

The effect of environment, diet, and digestive strategy on the microbiome of prickleback fishes (Family Stichaeidae)
Michelle Herrera and Donovan P. German
Dept. of Ecology and Evolutionary Biology, Charlie Dunlop School of Biological Sciences

Project Summary

Although fishes comprise the majority of vertebrates, the gut microbial ecosystem of marine fishes is relatively unknown compared to humans and domesticated animals. Some herbivorous fishes rely on microbial digestion to uptake nutrients. In the family Stichaeidae, there are two herbivorous species, Cebidichthysviolaceus and Xiphister mucosus, that differ in digestive strategies. Therefore, we aim to examine the microbiome of C. violaceus and X. mucosus and to investigate if the microbiome can shift with diet and/or digestive strategy. Metabolomics will be used to examine the underlying biochemical activity and differences in microbial metabolism. These molecular methods will give us a detailed insight into the diversity and characteristics of prickleback fishes intestinal ecosystem. Understanding what an animal eats and gives back to their environment combined with understanding their post-ingestive processes is crucial to providing insight into their role in the ecosystem.

The impact of Rhodiola rosea and metformin on the gut microbiome of leptin receptor (Leprdb/Leprdb) homozygous knockout mice
Mahtab Jafari
Dept. of Pharmaceutical Sciences, College of Health Sciences

Project Summary

In this project we will evaluate the impact of Rhodiola rosea and metformin on the gut microbiome of a severe obese and diabetic mouse model, leptin receptor (Leprdb/Leprdb) homozygous knockout mice. Both Rhodiola rosea and metformin have shown to increase the lifespan and improve the healthspan of various model species and are considered anti-aging mimetics. Metformin is a well-established anti-diabetic drug and will serve as the positive control in this project. We hypothesize that Rhodiola rosea will improve the biomarkers of health such as glucose and insulin tolerance tests and change the gut microbiome in this severe diabetic and obese mouse model.

Elucidating the role of the local and global microbiome in the development of alopecia areata
Margit Juhasz and Natasha Mesinkovska
Dept. of Dermatology, School of Medicine

Project Summary

Alopecia areata (AA) is an autoimmune, inflammatory, non-scarring disease that selectively attacks the hair follicle causing hair loss ranging from patches in the scalp (AA) to the entire scalp (alopecia totalis/AT), and even the entire body (alopecia universalis/AU). The condition is associated with a high level of psychological patient morbidity. The microbiome community contributes to human health through host defense mechanisms, inflammatory modulation and homeostasis mechanisms. Current research suggests that derangements in the resident microbiota may lead to diseases such as inflammatory bowel disease, allergy, and metabolic syndromes. Specific to dermatology and hair biology, new literature has demonstrated that the global microbiome may play a role in the development of AA. With this project we hope to characterize both the local scalp and global microbiota of alopecia areata patients versus healthy controls in an attempt to determine if there are significant differences in the make-up of the microbiome within these two groups.

Identifying Dysbiosis of the Skin Microbiome on Residual Limbs of Prosthetic Users
Hannah Keane and Katrine Whiteson
Dept. of Molecular Biology and Biochemistry, Charlie Dunlop School of Biological Sciences

Project Summary

The human microbiome, much like our fingerprint, is unique among individuals. Furthermore, there is significant intrapersonal variation among body sites. These complex microbial communities form distinct ecosystems across the body, some of which are of particular interest in the study of disease. I hypothesize that malodor forms at sites of prosthetic use in persons with amputations as a result of specific bacterial communities. This malodor may indicate a skin microbiome of aerotolerant organisms dominated by anaerobic bacteria. To this end, I expect Corynebacterium, Propionibacterium, Staphylococcus aureus, Staphylococcus epidermidis, and coagulase-negative Staphylococcus to be the most abundant species present, which contribute to the odor common among the residual limbs of prosthetic users, often leading to dermatitis. This study provides a non-invasive method for collecting host-associated bacterial skin samples from human volunteers. The purpose stands to characterize the microbial composition present at the site of socket wear, in order to understand the function of these communities of bacteria in dysbiosis and disease.

Microbiome diversity in patients with uveitis: influence of oral and gut microbiome on uveitis
Sanjay Kedhar
Dept. of Ophthalmology, School of Medicine

Project Summary

Uveitis is an inflammation of the inner layer of the eye and is the third-leading cause of blindness in developed countries. The majority of cases are classified as non-infectious, autoimmune uveitis and the underlying cause is not well understood. Recent animal studies have found that commensal bacteria in the gut influence the development of uveitis and that antibiotic treatment can diminish the severity of the disease. This project aims to characterize the diversity of the oral and gut microbiome and investigate the potential for differences in patients who develop uveitis versus similar patients who don’t. In characterizing the diversity of the microbiome before, during and after an attack of uveitis, we hope to understand the role that changes in the microbiome might play in the development of uveitis and ultimately to find alternative therapies to treat these diseases.

The Role of the Microbiome in Seagrass Digestion in the Omnivorous
Samantha C. Leigh and Donovan P. German
Dept. of Ecology and Evolutionary Biology, Charlie Dunlop School of Biological Sciences

Project Summary

The bonnethead shark (Sphyrna tiburo) is the only known shark species to consume copious amounts of seagrass (up to 62% of their diet in some populations). To date, we have established that S. tiburo are capable of digesting and assimilating seagrass nutrients, and we have evidence suggesting that the mechanism by which this occurs involves microbial symbionts. Studies have shown that microbial communities vary with the diet of the host and therefore, it is likely that gut microbes affect digestive performance. Using 16S sequencing, I will identify microbes that are of potential importance to S. tiburo’s ability to breakdown seagrass. Investigations of microbial communities in the guts of teleost fishes reveal that herbivores generally have a greater diversity and abundance of microbes. Very few investigations have evaluated the microbiome of elasmobranchs, but given that S. tiburo is exhibiting omnivorous tendencies, their microbiome may be more diverse than strictly carnivorous sharks.

Investigating the contribution of bacterial diversity in the pathogenesis of HD
Ryan Lim and Leslie M. Thompson
Dept. of Psychiatry & Human Behavior, School of Medicine

Project Summary

Accumulating evidence shows a significant role of the microbiome in the manifestation and progression of neurological diseases. The gut microbiome-brain axis is a novel field of study whose overall contribution towards disease are unclear. The age of onset and progression of HD, like many other neurological disorders, is regulated by a multifactorial set of genetic and environmental contributors which could include the microbiome. Unlike several other diseases, the genetic cause of HD is established, however the mechanisms that contribute to age of disease onset is poorly understood. Elucidation of microbiome contributions towards HD will shed light on whether this novel system is playing a key role in the variance of onset, the mechanisms of the disease, and provide insight into health outcomes and comorbidities of HD and many other neurological diseases.

Analysis of human wound microbiome during negative pressure wound therapy
Wendy Liu and Timothy Downing
Dept. of Biomedical Engineering, School of Engineering

Project Summary

Impaired wound healing is a major clinical problem, and currently available treatment options fail to fully repair tissue. In dermal wounds, exposure to the environment often leads to bacterial and/or fungal infection, but how the microbiome influences wound repair and tissue healing remains mostly unknown. This goal of project is to characterize the microbiome in wounds undergoing negative pressure wound therapy, a clinical used treatment in which wounds are covered with a porous material and subjected to negative pressure, which mechanically stimulates the wound. We will investigate the effect of NPWT itself as well as the different biomaterials used on the microbiome. This work will be performed in conjunction with longitudinal characterization of local cytokines and immune cell infiltrates in the wound bed, and will help to develop correlations between microbiome and the overall wound healing process. We hope to use insights gained from these studies to enable the design of novel strategies to improve NPWT.

DSS-induced gut inflammation increases the risk of Parkinson’s disease in rats carrying human LRRK2-G2019S mutation
Sudhakar R. Subramaniam, Massino S. Fiandaca, and Howard J. Federoff
Dept. of Neurology, School of Medicine

Project Summary

Parkinson’s disease (PD) is a human condition characterized by the progressive loss of dopamine neurons (DANs) in the brain. One million people in the Unites States have PD, with 10% caused by specific gene mutations while most (~90%) cases occur sporadically. The majority of sporadic PD cases likely result from harmful interactions between certain genes and a variety of environmental factors. A relatively common gene mutation LRRK2 (leucine-rich repeat kinase 2) G2019S has been associated with both familial and sporadic PD. Our laboratory has generated rats harboring a human BAC with mutant LRRK2-G2019S or a human BAC with the wildtype LRRK locus on a genetic background lacking rat LRRK2 mutation. Administration of LPS (IP) in mutant but not wildtype human LRRK promotes a PD-like DAN loss and movement abnormalities. We aim to expose our hLRRK2-G2019S and wildtype hLRRK2 rats to an oral solution that induces inflammation/infection in the colon. We plan to investigate the effects caused by the LRRK2-G2019S mutation and colonic inflammation on gut microbiome characteristics, the impact on midbrain DANs, and animal behavior.