The overall goal of the present proposal is to begin to reveal presently unknown interactions between host and oral microbiome in the context of smoking and drinking behaviors. The oral microbiome plays a relevant role in determining the risk of several pathologic conditions (e.g., upper aerodigestive tract cancers, cardiovascular diseases, and inflammatory bowel diseases). Drinking and smoking behaviors have been also demonstrated to affect the oral microbiome ecosystem. The human-microbial oral interactome is likely the most important determinant of physiological and pathological conditions related to the oral microbiome, but to our knowledge no genome-wide investigation has been performed. This lack strongly encourages us to deepen the understanding of the genetics of host-microbiome interaction, and smoking and drinking behaviors represent strong candidates as relevant modulators of human-microbial oral interactome. We propose to perform a genome-wide investigation of the oral microbiome in the context of smoking and drinking behaviors.
AIM 1: Detect the oral microbiome associated with smoking and drinking behaviors. We will analyze the oral microbiomes of subjects with alcohol and nicotine dependence (i.e., extreme smoking and drinking behaviors) and compare these results with the oral microbiomes of comparison subjects from general population (i.e., uBiome reference data).
AIM 2: Identify loci associated with the smoking and drinking behavior-related oral microbiome. We will perform a genome-wide investigation of the drinking and smoking-associated microbiome, also evaluating the impact of smoking and drinking behavior on the identified candidate associations.
AIM 3: Investigate the human-microbial oral interactome. We will use the results of the genome-wide investigation and the information about protein-protein interactions to identify molecular pathways involved in the human-microbial oral interactome of subjects with alcohol and nicotine dependence.
Why This Project?
To date, scientific research is regulated by policies that make it hard to find the funds necessary to start novel research investigations without consistent preliminary results, especially when these proposals are from young investigators. As described above, the present proposal is solid and very innovative and we have a strong background in genome-wide investigations of human behaviors that give us the expertise to carry out the investigation proposed. However, applying for exploratory grants without preliminary results and the scientific background on microbiome research may be very frustrating.
The uBiome grant will fast-track our exploratory study of the genetic basis of human-microbial oral interactome in the context of drinking and smoking behaviors. This first investigation will produce the preliminary results that are necessary to apply for further grants that will permit us to deepen the interplay between human behaviors and microbiome and its effect on human health. The uBiome grant contest is seeking researchers to sail boldly off into uncharted waters in a spirit of curiosity and adventure. Our research group fits that description since our proposal can open a new way to look both human microbiome and human behaviors with the aim to generate high-impact applications to improve human health. Most succinctly – it is an important project; and we will work hard and get the job done; we have a track record showing that we can do this.
About the Researcher
Dr. Renato Polimanti is a genetic epidemiologist with a wide range of interests, including biological psychiatry, evolutionary biology, medical genetics, and computational biology. He began his career in science as PhD student in the group of Prof. Maria Fuciarelli at the University of Rome "Tor Vergata". The main research interest of Prof. Fuciarelli’s lab is anthropological genetics. However, he developed his PhD studies, not only focusing on population genetics (Polimanti et al., 2015 Eur J Hum Genet) but also working on projects related to medical genetics (Polimanti et al., 2014 Amyloid; Polimanti et al., Fertil Steril 2012) and neuroscience (Squitti, Polimanti et al., 2013 Neuromolecular Med). These experiences permitted Dr. Polimanti to successfully complete his PhD program with a thesis about the evolution of pharmacogenetic systems in worldwide populations and its effect on human health (Polimanti et al., 2011 Pharmacogenet Genomics; Polimanti et al., 2012 Pharmacogenomics; Polimanti et al., 2013 Pharmacogenomics; Polimanti et al., 2014 Pharmacogenomics). In November 2013, Dr. Polimanti joined as postdoctoral associate the lab of Prof. Joel Gelernter in the Division of Human Genetics of the Department of Psychiatry at the Yale University School of Medicine. Here, his research interests are the genetics of behavioral phenotypes, including substance dependencies, pathologic gambling, sexual behaviors, childhood adversity, and post- traumatic stress. His initial investigations provided novel findings regarding the role of ancestry in genome-wide association study of substance dependencies (Polimanti et al., 2015 Pharmacogenomics) and the molecular mechanisms by which alcohol dependence affects body mass regulation (Polimanti et al., 2015 Addiction Biology).