Participating Departments

Molecular and Biomedical Pharmacology
***
Molecular and Cellular Biochemistry
***
Anatomy and Neurobiology
***
Pharmaceutical Sciences
***
Department of Psychology

A critical aspect of the training program is that modern techniques such as structural biology, proteomics, and microarray technology are used in conjunction with molecular biology, pharmacology and basic neuroscience to explore the mechanisms that are the foundation of drug abuse research.  The training program provides the opportunity for predoctoral trainees to understand the normal and pathological functioning of the systems involved in their research and to apply state-of-the art techniques to their studies.  Through the research programs of the training faculty and the core facilities at UK, this program offers a variety of research areas and approaches related to the actions of drugs of abuse.  In addition, working together with the strong training program in the psychological and behavioral aspects of drug abuse at UK, our trainees are exposed to both molecular as well as behavioral aspects of drug abuse research.  Thus the scope of training extends beyond molecular, structural and cell biology, to systems and psychosocial levels of analysis. 

Since graduate students do not pick a mentor or research project until after their first year in residence predoctoral trainees are not appointed to the training program until after their first year of studies is complete.  The first year of graduate school involves a broad based curriculum exposing students to basic concepts in the basic sciences and includes at least four research rotations.

The integration of interdisciplinary approaches such as molecular biology, biochemistry, neurobiology, physiology, pharmacology, and structural biology are necessary to determine the complex mechanisms by which drugs of abuse modify receptors and alter enzymes and other components of the nervous system that regulate neurotransmission and behavior.  The University requires each graduate student to have a thesis committee comprised of at least four individuals.   Multidisciplinary and translational research is encouraged and developed through their thesis advisory committees with a goal of leading to new drug abuse related research proposals submitted to NIDA.

Trainees receive their degree from individual departments and as such must meet the requirements of their departmental programs.  In addition all trainees participate in a the course, entitled “Molecular Neurobiology of Abused Drugs”, which can be substituted for a departmental requirement.  A perhaps unique aspect of the proposed training program is the exposure of the trainees to the psychological and behavioral aspects of drug abuse.  This is accomplished through the participation of trainees in the course “Biobehavioral Perspectives on Drug an Alcohol Abuse and Dependency” taught through the Behavioral Sciences training program.  In addition, trainees attend relevant seminars sponsored through the Center on Drug and Alcohol Research (CDAR) and the Center on Drug and Alcohol Research Translation (CDART).  Members of the drug abuse training program in Behavioral Sciences participate with our trainees in an annual symposium described in this proposal with recent programs provided in the appendix.  Our trainees as well as those from the behavioral science training program also participate in a monthly evening get-together with refreshments referred to as “Local NIDA” (Univ. Kentucky Neuroscientists Interested in Drug Abuse).  This has been ongoing for more than 30 years.  Attendance often includes 30+ individuals —including predoctoral students, postdoctoral scholars, interested staff, and faculty from all disciplines of drug abuse research.  The informal setting of these get togethers allows students and postdoctoral fellows to present their research findings in a “friendly” environment and is a forum, which encourages new, not yet ready for primetime results to be discussed.  Often invited seminar speakers from outside the University participate in this forum.

List of recent “Local NIDA” meetings:

Another less formal mechanism for training and interaction is through the UK Local Chapter of the Society for Neuroscience.  The Chapter includes over 200 members, and each year the Chapter sponsors a Spring Poster Presentation Day in which graduate students and postdoctoral fellows present their recent findings in a competition for best poster award.  An eminent neuroscientist is also invited to give a keynote seminar, and time is provided for the speaker to interact with students and postdoctoral fellows at a Chapter-sponsored lunch.  This past year, a record number of posters were presented and lively discussion ensued.

Together these activities provide an excellent environment for cross-fertilization of the research being conducted on the behavioral and psychological aspects of drug abuse with the molecular approach to drug abuse research stressed in this training program.  Thus, students and postdoctoral scholars who receive training through this program get a unique broad-based perspective of drug abuse not readily available to basic biomedical researchers, and will be well equipped to develop an independent research program based on a broad perspective of problems related to drug abuse.

As mentioned above a new course in drug abuse was introduced and will continue to be a requirement for all trainees.  The following are the topics presented in this course this past year:

·      Orientation to molecular and cellular mechanisms of drug abuse and dependence

·      Drug abuse during neural development – prenatal and adolescent nicotine and cocaine exposure

·      Drug disposition: Pharmacokinetic concepts relevant to abused drugs

·      Molecular and cellular mechanisms/adaptations of psychostimulant abuse: methamphetamine

·      Molecular and cellular mechanisms/adaptations of cannabinoids abuse Guest lecturer – Sandra Welch, Virginia Commonwealth University

·      Molecular and cellular mechanisms/adaptations of psychostimulant abuse: cocaine

·      Molecular and cellular mechanisms/adaptations of opioid abuse

·      Molecular and cellular mechanisms/adaptations of psychostimulant abuse: nicotine

·      Molecular and cellular mechanisms/adaptations of alcohol abuse

·      Modeling and structural contributions: nicotinic receptors Guest lecturer - Palmer Taylor, University of California San Diego.

·      Modeling and structural contributions: opioids

·      Modeling and structural contributions: cocaine

·      Neuropathogenesis of drugs of abuse

·      Drugs of abuse and interaction with HIV/AIDS

·      Development of novel pharmacotherapies for the treatment of drug abuse: cannabinoids

·      Development of novel pharmacotherapies for the treatment of drug abuse: methamphetamine or opioids

As noted above many of our predoctoral students enter graduate school and participate in an Integrated Biomedical Sciences (IBS) First Year Curriculum.  This curriculum is given below:

      Fall Semester                                                                                         Spring Semester

Biomolecules and Metab.(3 hr)                             Biomolecules and Mol. Biol (3 hr)

Cell Biology (3 hr)                                                                            Cell Signaling (3 hr)

Experimental Genetics (2 hr)                                             Integrated Biomedical Sc. (4 hr)

Seminar (0 hr)                                                                                              Seminar (0 hr)

Research Rotations (1 hr)                                                  Research Rotations (1 hr)

Typical Second Year Curriculum

      Fall Semester                                                                                         Spring Semester

Human Medical Neurosc. (3 hr)                            Molecular Neurobiol. (3 hr)

*Department Elective (3 hr)                                                *Department Elective (3 hr)

Research(3 hr)                                                                                             Research (3 hr)

Seminar (1 hr)                                                                                              Seminar (1 hr)

* Departmental electives are chosen from the course listings given below.

In year 3 students spend the majority of their time conducting their dissertation research.  They will also participate in the course Biobehavioral Perspectives on Drug and Alcohol Abuse and Dependency as well as participate in the seminar series “Behavioral and Neural Psychology” and the Neuropharmacology Journal Club.

Description of The First Year Integrated Biomedical Sciences Courses.

Note: First year graduate students participate in the integrated curriculum and then select a mentor at the end of the first year.  Thus eligible trainees will be admitted to the training grant in their second or subsequent years.  The following courses, noted as IBS courses, are the ones taken prior to their acceptance in the proposed program.

      Biomolecules and Metabolism (IBS601) and Biomolecules and Molecular Biology (IBS602).  IBS601 is the first semester of a year-long course introducing graduate students to the molecules that comprise biological systems, the principles governing their behavior, and the methods used in their study.  Basic aspects of carbohydrates and lipids are covered as well as protein structure and function and metabolic control.  The text is Voet and Voet.

      IBS602 is the second semester of the year-long course and is designed to provide graduate students with the foundation of knowledge in molecular biology (concepts and techniques) necessary for advance graduate study and research.  The course focuses primarily on the cellular mechanisms that underlie the regulated expression of genes, including transcription and translation, as well as basic mechanisms of DNA replication/repair and recombination.  In addition, genetic engineering and other experimental approaches that are critical to molecular biology research are reviewed.  Course material is presented in a number of formats, consisting primarily of didactic lecture by expert faculty, but also is reinforced by group discussions of selected readings and exercises.  The text is Molecular Biology of the Cell, by Alberts, et al.  Additional readings from the scientific literature are provided.

      Cell Biology (IBS603)  IBS603 consists of lectures relating to cell types and architecture, membrane structure, cytoskeleton, mitochondria, cellular mechanisms of development, cell division, cell cycle, apoptosis, necrosis, and cancer, as well as other topics.  This course involves a series of approximately 4-5 lectures followed by a discussion session/journal club.  The class period will entail discussion of 1-2 questions that are assigned by course faculty prior to class.  During the discussion sessions, students are asked to present their answers to the questions.  The text, Molecular Biology of the Cell, 4^th Edition, Alberts et al. is used as well as supplemental paper/review articles.

      Experimental Genetics (IBS605)  IBS605 is designed to provide graduate students with the foundation of knowledge in classical and molecular genetics necessary for advanced graduate study and research.  The course focuses primarily on basic genetic principals, prokaryotic genetics, eukaryotic genetics, and genomics.  The course also covers contemporary topics including human genetics and bioinformatics.  In addition, experimental approaches in genetic research are reviewed.  Course materials are presented in both didactic lectures and discussions of selected readings and bioinformatics small-group sessions.

      Integrated Biomedical Sciences (IBS606)  IBS606 considers function of the mammalian organism from a perspective ranging from the cellular/sub-cellular to the organ system and whole organ.  It capitalizes upon the IBS series of courses to allow graduate students to develop a truly integrative appreciation of biologic function.  The course is organized into four basic sections that include (a) the organization and function of the nervous system, (b) control and integration of visceral function, (c) endocrine/neuro-endocrine contributions to homeostasis, and (d) immune function.  Each section culminates in the consideration of a pathological condition (Alzheimer’s disease, hypertension, diabetes and AIDS-cancer), which is intended to exemplify the body’s integrative response to a disease state.  The majority of course content is presented by didactic lectures supplemented with at least one discussion session/journal club per section.  Discussion sessions entail discussion of questions assigned by course faculty prior to the class and/or of papers chosen by the faculty or students. 

Laboratory Rotations (IBS609 and IBS610) and Student Seminars (IBS607 and IBS608)  Each semester the graduate student performs 2 laboratory rotations with a faculty member of their choice for the purposes of learning research techniques.  In addition students attend the student seminar program of the department in which they are conducting their laboratory rotation.  Although the students do not present a seminar during their first year they are expected to participate in the seminars by reading the papers being presented and participating in discussion of the papers.  At the end of the first year the student chooses a thesis laboratory.  It is at this point that a student could be appointed to this training program.  Such students would then take advanced courses that will best prepare them for a research career in areas related to neuroscience and drug abuse research.  Such courses would include:

Advanced Graduate Courses.

Advanced Cell Biology (BIO 632)  This course presents a molecular level treatment of cell structure and function derived from current experimental approaches.  Eukaryotes will be stressed. Topics will usually include membrane structure and function, the cytoskeleton and the extracellular matrix, and bioenergetics.

Advanced Molecular Pharmacology (PHA649)  This course is designed to provide an in-depth coverage of the molecular pharmacology of growth factors, transcription factors, receptors, and ion channels.  Emphasis will be placed on both the normal functions of these cell-signaling molecules and perturbations that result in several prevalent human diseases, including cancer, Alzheimer's, diabetes, osteoporosis, and inherited human illnesses.  Students will be introduced to experimental approaches to diagnosing and treating these illnesses in the light of our evolving knowledge of molecular pharmacology.

Advanced Neuropharmacology (PHA658)  This course focuses on a study of the general theories of the mode of action of drugs upon nervous tissue and a review of the effects of analgesics, sedatives, hypnotics, anesthetics, tranquilizers, psychotomimetics, analeptics, antidepressants, anti-convulsants, and drugs affecting motor dyskinesias upon neurones, synapses, and functional components of the central nervous system.

Advanced Neurophysiology (PGY 606)  The objective of this course is to study current problems and controversies in neurobiology and clinical neurology.  The course covers a variety of illnesses including epilepsy, neurodegenerative diseases, stroke, psychiatric illness, pain, diseases of immune origin, motor dysfunction and inherited disorders.

Biochemistry and Cell Biology of Nucleic Acids (BCH 611)  A lecture and seminar course devoted to a study of the principles of nucleic acid chemistry and to the role of nucleic acids in cellular function.

Biochemistry of Lipids and Membranes (BCH 610)  A lecture and seminar course devoted to intermediary metabolism of lipids and various biochemical aspects of the structure, assembly and functions of biological membrane systems.

Drug Targets and Actions (PHR760)  The objective of this course is to give students an overview of drug design, drug targets and actions.  More emphasis will be placed on drug design, structure and function of drug targets, and interactions of pharmacophores and drug targets.

Human Medical Neuroscience (ANA 636)  This course is an integrated neuroscience course introducing fundamental neural cell biology, neuroanatomy, systems neuroscience, neurophysiology and clinical applications.  This has a laboratory component, which includes neuroanatomical sections, and exposure to neuropathology, CT, Magnetic Resonance Imaging, and PET imaging. 

Introduction to Human Neuroscience (ANA516)  This course augments the Human Medical Neuroscience course by stressing additional current cell, and molecular, and neuropsychological concepts that are important for Neuroscientists.

Molecular Neurobiology (ANA/PGA618)  This course provides the knowledge base and analytical skills in the field of molecular neurobiology. An in-depth introduction to current technologies, their rationale and limitations, are the focus and address normal brain function and neuropathological conditions.

Molecular Neurobiology of Abused Drugs (PHR 7601)  This course is designed to introduce the student to topics relevant to modern drug abuse research.  It will cover a broad range of topics through didactic lectures, assigned readings from the literature, and class discussions.  (The proposed topic are noted above).

Molecular Pharmacology. (PHR 649)  This course is focused on the molecular aspects of a variety of physiological systems that are subject to pharmacological manipulation.  Emphasis is on the molecular genetics, biochemistry and subcellular organization and biology of these systems, and on the pharmacological techniques used to study them. Genetic diseases associated with these systems will also be described.

Neurotoxicology (PHR645)  Multidisciplinary discussions of the major sites and mechanisms of drug/chemical-induced nervous-system toxicity.  The toxic effects of  abused drugs on the nervous system is particularly emphasized.

Quantitative Pharmacodynamics (PHR612)  Quantitative treatment of dynamics of drug absorption, distribution, metabolism and excretion, including development of both mathematical models and model-independent approaches for describing these processes.

Structural Biology  (BCH604)  An advanced course on the structure and function of proteins and nucleic acids.  Topics include: the physical determinants of protein structure, classification of protein architecture, protein-nucleic acid and protein-protein interactions, sequence dependence of nucleic acid structure, ribozymes, dynamics, drug design, protein engineering, and evolutionary relationships.  Students are required to complete problem sets that involve use of computer databases and web based services, specialty structural biology software, graphics workstations, and the literature.

Structure and Function of Proteins and Enzymes (BCH 612)  Primarily a lecture course devoted to the relationship of the structure of protein molecules to their biological roles. Proteins will be discussed in terms of their size, shape, conformation, primary structure, catalytic mechanism and regulatory properties.

The Practice of Drug Metabolism (PHR760)  The purpose of this course is to teach students about practical aspects of drug metabolism research.  This includes addressing the function and purpose of drug metabolism studies, how those studies are carried out, why and how they are done, how metabolites are characterized, and some discussion of the limits and utility of the various approaches used in drug metabolism research.  The first part of the course deals with metabolite characterization, both the identification by NMR and MS, and isolation methods by chromatographic methods.  The second part of the course focuses on quantification and qualification methods employed in drug and metabolism research.  This includes analytical assay methods, mass balance studies, in vitro methods, autoradiography, and metabolite pharmacokinetics and toxicokinetics. The third section covers selected topics in drug metabolism research that are more topical and address issues related to drug metabolism research (pharmacogenomics, stereoselective metabolism, reversible metabolism, biomarkers and surrogate markers, microdialysis, unstable and reactive metabolite identification, High throughput analysis systems, computational systems).

Topics in Pharmaceutical Sciences (PHR 760)  This comprehensive course/journal club includes in depth discussions on many different aspects of nervous system pharmacology.  Topics covered related to drug abuse include psychostimulants [e.g. cocaine, methamphetamine, nicotine], opioids, cannabinoids, MDMA, benzodiazepines and alcohol.

In addition to didactic coursework trainees participate in their departmental student seminar program, faculty seminar program for invited speakers, and journal clubs.  As part of the departmental seminar programs students meet with and interact with invited speakers through either a lunch meeting, as part of a group meeting, or in a one on one setting.  These meetings often lead to collaborative and/or postdoctoral opportunities for the students.

The training program hosts an annual symposium involving a seminar given by a world-renowned scientist working in the area of drug abuse or a related field.  As part of the symposium students present their research in an oral presentation format, and host a lunch or dinner for the invited lecturer.  As noted above this symposium is held jointly with the trainees from the training program focused on the behavioral aspects of drug abuse.