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Opioid Dependence Vulnerability in a Rodent Model

  • Full or part time
  • Application Deadline
    Thursday, February 28, 2019
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Substance abuse disorder (SUD) is a global problem that affects the health, social and economic welfare of all societies (1). Opioid use disorder (OUD) is characterized by compulsive use of opioids despite adverse consequences from continued use and the development of a withdrawal syndrome when opioid use ends (2). Young adults that are depressed and have SUD are more likely to have a low socioeconomic status (3). Parallels between drug addiction and eating behavior have resulted in food addiction and obesity now being categorized as a neurobehavioral disorder. Endogenous opioids regulate eating behavior, signal satiety and maintain long-term energy balance. Opioid antagonists attenuate addictive drug taking and appetite. Thus, craving for palatable food is an opioid-related addiction (4, 5). SUD involves a complex interplay of genetic, epigenetic and host–microbiome interactions (6,7). The goal of this PhD project will be to exploit the outbred (NIH/H) rat model of opioid abuse currently being developed as part of the US NIH U01DA045300 award (Hardiman, QUB PI) and carry out transcriptome (RNA) and epigenetic (miRNA/methylation) experiments on neural tissues & blood in addition to metagenomics on fecal matter from vulnerable and resilient animals. Systems level modeling on these data will provide novel insights into the basis for food addiction.

Specific skills/experience required by applicants:

Molecular biology skills, experience working with high dimensional genomic data, such as sequencing data, gene expression, genotype, CNV, sequence and/or data from other high throughput biological technologies desired. Programming skills in a high level language especially Python and/or R. Experience with Linux shell scripting desirable.

Funding Notes

Only UK and EU students are eligible to apply. Information on eligibility criteria is available from DfE: View Website

References

1. Uhl GR. Molecular genetic underpinnings of human substance abuse vulnerability: likely contributions to understanding addiction as a mnemonic process. Neuropharmacology. 2004;47:140-7.

2. Kreek MJ, Nielsen DA, Butelman ER, LaForge KS. Genetic influences on impulsivity, risk taking, stress responsivity and vulnerability to drug abuse and addiction. Nature neuroscience. 2005;8(11):1450-7.

3. Dagher RK, Green KM. Does depression and substance abuse co-morbidity affect socioeconomic status? Evidence from a prospective study of urban African Americans. Psychiatry Res. 2015 Jan 30;225(1-2):115-121.

4. Cornelis, Marilyn C., et al. "A genome‐wide investigation of food addiction." Obesity 24.6 (2016): 1336-1341.

5. Gosnell, B. A., and A. S. Levine. "Reward systems and food intake: role of opioids." International journal of obesity 33.S2 (2009): S54.

6. Renthal W, Nestler EJ. Epigenetic mechanisms in drug addiction. Trends Mol Med. 2008;14(8):341-50.

7. Xu, Yu, et al. "Bacterial diversity of intestinal microbiota in patients with substance use disorders revealed by 16S rRNA gene deep sequencing." Scientific Reports 7.1 (2017): 3628.

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