Topic outline

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  Course outline

  Detailed Course Outline  

  Title::Molecular Biology: Molecular basis of diseases

  Course code: ZOO 414.2

  Date active:01.01.2018

  Unit Type: Optional Course 

  No of notional hours: 100

  Attendance: 80% attendance

  No: of tutorial hours: 2

   

  Module aim: The aim of this course is to explore the molecular mechanisms behind some of the diseases that are encountered within our society. These are diseases that are serious in nature and are not presently “curable,” with intensive research currently being conducted worldwide to battle these deleterious conditions. Basic principles of extracellular and intracellular signaling systems will also be included. We will discuss some of the therapies used to treat these diseases, with emphasis on the molecular pathways that are utilized during treatment. Methods of DNA analysis, gene technology will also be discussed.

  This course will impart students with critical reading and scientific papers. Students will read 4-5 papers from the primary research literature before coming to each class. This reading is essential since the class discussion will be based on these materials. 

   

   Intended Learning Out Comes: Upon successful completion of this course students will be able to 

  • identify common diseases and molecular basis with a significant molecular basis.
    
  • Demonstrate how inheritance of mutated genes leads to pathology either in childhood or in later life.
    
  • Interpret how the lifestyle of an individual or his/her environment can give rise to genetic or physiological change within the adult cell that results in diseases.
    
  • Discuss how the rational design of novel therapies can arise from knowledge of the molecular basis of disease.
    
  • Discuss and orally present scientific papers within the field of molecular diseases.
    
  • Acquire soft skills such as leadership, communication, presentation, interpersonal skills, and competence in independent working.
    
  • Give and receive feedback in productive ways. 
    
  • Engage in academic and professional communication with others. 
    
  • Adapt learning strategies to overcome difficulties and produce the quality of work required. 
    
  • Search, access, evaluate, and select information from a range of IT services. 

  Prerequisites:  Cell Biology, Genetics, Physiology, Molecular Biology

  Course Description: Molecular Basis of and mechanisms of selected common diseases including cardiovascular disease, diabetes, cancer, Ion channels disease, muscle diseases, neurodegeneration, thrombosis, and metabolic diseases.Use of Molecular Knowledge for Diagnosis

  Assignment:    15 min individual presentations.

                           Examination based on selected research paper

                           Journal club

          Must complete the assignment 1 to sit for the final exam.

  Methods of Assessment:          1. News and Views (1000 words)                      (20%)

                                                      2. Case study on gene mutation                        (10%)

                                                       3. Journal club                                                       (10%)

                                                       4.One  hour final exam                                    (60%)

  Skills developed by students: 

  • Presentation skills develop competence in independent research and skills as a critical learner using high-quality literature;
    
  • engage in academic and professional communication with others;
    
  • cultivate problem-solving skills and reflection on personal responsibility in professional practice.
    
  • Adapt learning strategies to overcome difficulties and produce the quality of work required. 
    
  • Give and receive feedback in ways that are productive. 
    
  • Communicate sources of information appropriately eg references, bibliographies. 
    
  • Search, access, evaluate, and select information from a range of IT services. 

  Recommended Reading:John Macloed (1988). Davidson’s principles and Practice of Medicine., 24th Ed. Churchill Livingstone, Snustad, D.P. & Femmans, 

  Gillham, B., Despo, K.P., Thomas, J.H. (1997). Will’s Biochemical Basis of Medicine., Reed Educational and Profesional Publishing Ltd. 

  E-books will be uploaded to google classroom 

   Web resources:  Different research articles 

   

  Course specification and conduct

  The course will be composed of two lectures per week. Students are expected to complete assigned readings prior to class. We will discuss 9-10 primary literature papers. All students should be ready to participate in class discussions and to provide, when required, a short written assignment that will be due at the beginning of the paper discussion. See google classroom and notice boards for Exam and Lecture Schedule. A separate document lists specific lecture topics and dates, including due dates for assignments and exams. 

  It is important that you read the assigned materials before you come to the lecture. The exams will cover both lecture and assigned reading materials. 

  All information for the course will be posted on Google classroom. I will also send announcements and information. 

  Primary literature discussions: Please read the assigned research papers and be prepared to discuss them in class. Articles from the research literature are available for download from Google classroom. 

  You will be assigned to a group responsible for presenting a research paper (the full group assignment list will be posted in Blackboard after the first week of class). Each person will work with his/her group to organize the presentation. Everyone in the group is required to participate (e.g., present a figure, introduce the paper, or explain a technique). The figures and tables will be provided in class as a Keynote or Powerpoint file for projection. Any additional materials you plan to use should be provided in advance (preferable) or brought to class in a separate Powerpoint file. Presentations should be organized as follows: 

  Introduction: Describe the major question, problem, or technical issue addressed in the paper. Explain relevance and background information, including previous work. You are encouraged to briefly discuss other relevant articles from the literature. 

  Results: Explain the results and how they were obtained. Refer specifically to data in the figures and/or tables. This will entail discussing the methods used (refer to the Methods section of the paper). 

  Discussion: Summarize and explain the significance of the work presented in the paper. You are encouraged to briefly discuss other relevant articles from the literature. 

  Questions: The rest of the class is expected to participate in the discussion by asking questions regarding the article being presented. Members of the group should be prepared to answer questions about the results and/or clarify techniques employed in the study. 

  ONLY WHEN ASSIGNED, you will have to write a summary of the article (no longer than two double- 

  spaced pages; worth a total of 10 points) that should include: 

  A description of the major question, problem or technical issue addressed in the paper (2 points) 

  Identification of the hypothesis or idea leading the authors to perform the experiments described (2 points) 

  Selection and explanation of the experiment you think is the most important or interesting (2 points) 

  Identify any future or unanswered questions (2 points) 

  A proposal of a hypothesis to explain this new question(s) or identification of experiments that could address unanswered questions presented in the article (2 points) 

  Examples of this type of summary will be posted on Google classroom. 

  Total notional hours (100 h)
  Active hours: Lectures:             22 h

  Preparation for presentations      20 h

  Presentations/journal club:          20 h

  Mid exam:                                 1 h 

  Final exam:                                 2 h 

  Independent study hours:           30 h

  
  

  Academic Integrity

  Students are expected to be honest and ethical in their academic activities. If a student deliberately does the copying, cheating or plagiarizing, he or she may be penalized based on the University rules and regulations concerning such acts of academic misconduct. Please read the FAS code of conduct related to academic integrity. 

  The FAS has firm rules governing academic misconduct and there are substantial penalties that can be applied to students who are found in breach of these rules. Academic misconduct includes, but is not limited to:

                                  i.     Plagiarism; 

                                 ii.     Unauthorized collaboration; 

                                 iii.    Cheating in examinations; 

                                 iv.    Theft of other students’ work. 

  Additionally, any material submitted for assessment purposes must be work that has not been submitted previously, by any person, for any other unit at Department or elsewhere.

  Student Feedback        

  At the end of the lecture series and practical series, students are requested to fill a standard questionnaire to obtain the feedback on lecturers and laboratory classes

  Tentative topics are shown below. However, topics can change. Changes will be posted in google classroom

  Week 1	Introduction and requirements, Introduction to diseases. Apoptosis, Cancer
  Week 2	Thalassemia paper discussion from the literature
  Week 3	PKU (Phenylketonuria)– paper discussion
  Week 4	Obesity Paper discussion
  Week 5	Assignments are due. Cardiovascular diseases and paper discussion
  Week 6	Student presentations / Journal club
  Week 7	Pulmonary diseases. Paper discussion
  Week 8	Cystic fibrosis. Paper discussion. Assignment due
  Week 9	Myotonic dystrophy Paper discussion
  Week 10	Leukemia. Paper discussion
  Week 11	Student presentations / Journal club
  Week 12	Debate on Gene Therapy
  Week 13	Diabetes Paper discussion
  Week 14	Student presentations / Journal club
  Week 15	Model paper discussion

   

  Students can meet me during the following hours

  Office hours – Monday to Wednesday 11.30 to 2.30 pm

   Teaching Learning Activities (TLA)

  • Teacher-student interaction/ lectures 
    
  • Self-studies
    
  • Problem-solving
    
  • Discussions
    
  • Review article analysis 
  • Presentations
  • Debates

  PLOs:

  • Demonstrate advanced knowledge and understanding of underlying concepts of respective subject areas
  • Acquire high levels of competence in practical/technical knowledge and skills for professional growth
  • Enhance the ability to communicate acquired knowledge, information, ideas, and solutions with clarity and coherence. 
  • Enhance emotional intelligence through social engagement, networking, and teamwork which leads to improved leadership qualities, respect for diverse points of view, and empathy and develop strategies to adapt to changing circumstances.
    
  • Develop cognitive and creative skills in identifying, collecting, and critically analyzing data and in solving problems independently.
  • Exercise personal integrity through responsibility and accountability and acquire professional integrity through inculcated entrepreneurial, managerial, and time-management skills. 
  • Demonstrate positive and healthy attitudes and values and engage in lifelong learning for the betterment of society. 

  Course blueprint 

  PLO#

  ILO1

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  ILO5

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  ILO8

  ILO9

  ILO10

  ILO11

  ILO12

  ILO13

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  PLO-ILO Map: summary 

  	ILO1	ILO2	ILO3	ILO4	ILO5	ILO6	ILO7	ILO8	ILO9	ILO10	ILO11	ILO12	ILO13
  PLOs	3	3	3	3	3	3	5	5	5	5	4	5	5

   

   

  Course blueprint (ILO-PLO-AS Map)

  PLOs	ILO1	ILO2	ILO3	ILO4	ILO5	ILO6	ILO7	ILO8	ILO9	ILO10
  1	ü AS1,AS2, AS5,AS6	ü AS1,AS2, AS5,AS6	ü AS1,AS2, AS5,AS6	ü AS1,AS2, AS6,AS7					ü AS1,AS2, AS6,AS7	ü AS3,AS8,
  2	ü AS1,AS2, AS5,AS6	ü AS1,AS2, AS5,AS6	ü AS1,AS2, AS5,AS6	ü AS1,AS2, AS5,AS6, A7, AS8,AS9	ü AS1,AS2, AS5, AS6, AS7, AS8, AS9	ü AS1,AS2, AS5, AS6,AS7, AS8,AS9	ü AS1,AS2, AS5, AS6,AS7, AS8,AS9	ü AS1,AS2, AS5, AS6,AS7, AS8,AS9	ü AS1,AS2 AS5,AS7,	ü AS1,AS2, AS5 AS6,AS7, AS8,AS9
  3				ü AS2, AS3 AS5,AS7, AS8,SA9	ü AS2, AS3 AS5,AS7, AS8,AS9	ü AS2, AS3 AS5,AS7, AS8,AS9	ü AS2, AS3 AS5,AS7, AS8,AS9	ü AS2, AS3 AS5,AS7, AS8,AS9	ü AS2, AS3 AS5,AS7, AS8,AS9	ü AS2, AS3 AS5,AS7, AS8,AS9
  4				ü AS2, AS3 AS5, AS7, AS8, AS9	ü AS2, AS3 AS5, AS7, AS8, AS9	ü AS2, AS3 AS5,AS7, AS8,AS9	ü AS2, AS3 AS5,AS7, AS8,AS9	ü AS2, AS3 AS5,AS7, AS8,AS9	ü AS2, AS3 AS5,AS7, AS8,AS9	ü AS2, AS3 AS5,AS7, AS8,AS9
  5				ü AS1,AS3, AS5,AS8	ü AS1,AS3, AS5,AS8	ü AS1,AS3, AS5,AS8	ü AS1,AS3, AS5,AS8	ü AS1,AS3, AS5,AS8
  6					ü AS2,AS3 AS4,AS8	ü AS2,AS3 AS4,AS8	ü AS2,AS3 AS4,AS8			ü AS2,AS3 AS4,AS8
  7				ü AS1,AS3 AS6,AS8 AS9	ü AS1,AS3 AS6,AS8 AS9	ü AS1,AS3 AS6,AS8 AS9		ü AS1,AS3 AS6,AS8 AS9	ü AS1,AS3 AS6,AS8 AS0	ü AS1,AS3 AS6,AS8 AS9

   

  ILO-TLA-AS Map

   

  ILO	ASs	TLAs
  Subject knowledge  (ILOs 1, 2, 3, 4, & 5)	Assignments Final exam Case study	Lectures Self-studies Discussions Presentations Journal clubs
  Cultivate the creativity, problem-solving skills, critical thinking, and reflection on personal responsibility in professional practice.	News and Views  Final exam Case study Journal club	Problem-solving  Presentations Self-studies Research article analysis/
  Acquire soft skills such as leadership, communication, presentation, interpersonal skills, and competence in independent working.	Presentations Journal club	Discussions Presentations Research article analysis  In-class debates
  Give and receive feedback in productive ways	Journal club	Presentations Debate Discussions Research article analysis
  Engage in academic and professional communication with others	Journal club	Discussions Research article analysis
  Adapt learning strategies to overcome difficulties and produce the quality of work required	Case study News & Views	Self-studies Problem-solving Research article analysis
  Apply known situations to an unknown scenario	Final exam Journal club	Research article analysis Debate Problem-solving
  Search, access, evaluate, and select information from a range of IT services.	Case study  Final exam Journal club	Research article analysis  Student-centered learning

   

  
  

  • Google Clasroom Link URL

    All the files will be upload in the google classroom 

  • Assignment 1- News and Views Article

    Select a research paper News and Vies article should be about 250 - 300 words only Check this website for an example.

      https://www.nature.com/articles/424143a
    

    Guidelines are given in the attached files 

• 

  Topic 1

  The Molecular Basis of Cancer arms you with the latest knowledge and cutting-edge advances in the battle against cancer. This thoroughly revised, comprehensive oncology reference explores the scientific basis for our current understanding of malignant transformation and the pathogenesis and treatment of this disease. A team of leading experts thoroughly explains the molecular biologic principles that underlie the diagnostic tests and therapeutic interventions now being used in clinical trials and practice. Detailed descriptions of topics from molecular abnormalities in common cancers to new approaches for cancer therapy equip you to understand and apply the complexities of ongoing research in everyday clinical application.

  • News forum
• 

  Topic 2

  The revolution in cancer research can be summed up in a single sentence: cancer is, in essence, a genetic disease. In the last decade, many important genes responsible for the genesis of various cancers have been discovered, their mutations precisely identified, and the pathways through which they act characterized.
• 

  Topic 3

  The assembly of HIV is relatively poorly investigated when compared with the process of virus entry. Yet a detailed understanding of the mechanism of assembly is fundamental to our knowledge of the complete life cycle of this virus and also has the potential to inform the development of new antiviral strategies. The repeated multiple interaction of the basic structural unit, Gag, might first appear to be little more than concentration dependent self-assembly but the precise mechanisms emerging for HIV are far from simple. Gag interacts not only with itself but also with host cell lipids and proteins in an ordered and stepwise manner. It binds both the genomic RNA and the virus envelope protein and must do this at an appropriate time and place within the infected cell. The assembled virus particle must successfully release from the cell surface and, whilst being robust enough for transmission between hosts, must nonetheless be primed for rapid disassembly when infection occurs.
• 

  Topic 4

  Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The disease is characterized by a wide variability of clinical expression. The cloning of the CFTR gene and the identification of its mutations has promoted extensive research into the association between genotype and phenotype. Several studies showed that there are mutations, like the delta F508 (the most common mutation worldwide), which are associated with a severe phenotype and there are mutations associated with a milder phenotype. However, there is a substantial variability in disease expression among patients carrying the same mutation. This variability involves also the severity of lung disease. Furthermore, increased frequencies of mutations are found among patients with incomplete CF expression which includes male infertility due to congenital bilateral absence of the vas deferens. In vitro studies of the CFTR function suggested that different mutations cause different defects in protein production and function. The mechanisms by which mutations disrupt CFTR function are defective protein production, processing, channel regulation, and conductance. In addition, reduced levels of the normal CFTR mRNA are associated with the CF disease. These mutations are associated with a highly variable phenotype from healthy individuals or infertile males to a typical CF disease. This variability in disease expression is associated with different levels of normally spliced transcripts.
• 

  Topic 5

  The rapid increase in the prevalence of type 2 diabetes (T2D) represents a major challenge for health care delivery worldwide. Identification of genes influencing individual susceptibility to disease offers a route to better understanding of the molecular mechanisms underlying pathogenesis, a necessary prerequisite for the rational development of improved preventative and therapeutic methods. The past decade has seen substantial success in identifying genes responsible for monogenic forms of diabetes (notably, maturity-onset diabetes of the young), and, in patients presenting with early-onset diabetes, a precise molecular diagnosis is an increasingly important element of optimal clinical care. Progress in gene identification for more common, multifactorial forms of type 2 diabetes has been slower, but there is now compelling evidence that common variants in the PPARG, KCNJ11 and CAPN10 genes influence T2D-susceptibility, and positional cloning efforts within replicated regions of linkage promise to deliver additional components of inherited susceptibility.
• 

  Topic 6

  Obesity has increased at an alarming rate in recent years and is now a worldwide public health problem. In addition to suffering poor health and an increased risk of illnesses such as hypertension and heart disease, obese people are often stigmatized socially. But major advances have now been made in identifying the components of the homeostatic system that regulates body weight, including several of the genes responsible for animal and human obesity. A key element of the physiological system is the hormone leptin, which acts on nerve cells in the brain (and elsewhere) to regulate food intake and body weight. The identification of additional molecules that comprise this homeostatic system will provide further insights into the molecular basis of obesity, and possibilities for new treatments.
• 

  Topic 7

  Atrophy occurs in specific muscles with inactivity (for example, during plaster cast immobilization) or denervation (for example, in patients with spinal cord injuries). Muscle wasting occurs systemically in older people (a condition known as sarcopenia); as a physiological response to fasting or malnutrition; and in many diseases, including chronic obstructive pulmonary disorder, cancer-associated cachexia, diabetes, renal failure, cardiac failure, Cushing syndrome, sepsis, burns and trauma. The rapid loss of muscle mass and strength primarily results from excessive protein breakdown, which is often accompanied by reduced protein synthesis. This loss of muscle function can lead to reduced quality of life, increased morbidity and mortality. Exercise is the only accepted approach to prevent or slow atrophy. However, several promising therapeutic agents are in development, and major advances in our understanding of the cellular mechanisms that regulate the protein balance in muscle include the identification of several cytokines, particularly myostatin, and a common transcriptional programme that promotes muscle wasting. Here, we discuss these new insights and the rationally designed therapies that are emerging to combat muscle wasting
• 

  Topic 8

  Hematopoiesis is characterized by a rapid,continuous turnover of cells.Normall,,production of specific blood cells from their stem cells precursors is carefully regulated according to body’s need.If the mechanism that control the production of these cells are disrupted ,the cells can proliferate excessively.Hematopoietic malignancies are often classified by cells involved.LEUKEMIA is a neoplastic proliferation of one particular cell type (granulocytes,monocytes,lymphocytes,or infrequently RBCs). Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow. It usually progresses quickly if it is not treated. The disease accounts for about 10,600 new cases of leukemia each year, and it occurs in both adults and children.
• 

  Topic 9
• 

  Topic 10

  The thalassemias are a group of inherited hematologic disorders caused by defects in the synthesis of one or more of the hemoglobin chains. Alpha thalassemia is caused by reduced or absent synthesis of alpha globin chains, and beta thalassemia is caused by reduced or absent synthesis of beta globin chains. Imbalances of globin chains cause hemolysis and impair erythropoiesis. Silent carriers of alpha thalassemia and persons with alpha or beta thalassemia trait are asymptomatic and require no treatment. Alpha thalassemia intermedia, or hemoglobin H disease, causes hemolytic anemia. Alpha thalassemia major with hemoglobin Bart's usually results in fatal hydrops fetalis. Beta thalassemia major causes hemolytic anemia, poor growth, and skeletal abnormalities during infancy. Affected children will require regular lifelong blood transfusions. Beta thalassemia intermedia is less severe than beta thalassemia major and may require episodic blood transfusions. Transfusion-dependent patients will develop iron overload and require chelation therapy to remove the excess iron. Bone marrow transplants can be curative for some children with beta thalassemia major. Persons with thalassemia should be referred for preconception genetic counseling, and persons with alpha thalassemia trait should consider chorionic villus sampling to diagnose infants with hemoglobin Bart's, which increases the risk of toxemia and postpartum bleeding. Persons with the thalassemia trait have a normal life expectancy. Persons with beta thalassemia major often die from cardiac complications of iron overload by 30 years of age.
• 

  Topic 11

  Hemophilia A is an X-linked hereditary bleeding disorder due to the deficiency of coagulation factor VIII (FVIII). According to the degree of FVIII deficiency, mild, moderate or severe forms are recognized. Although patients with mild hemophilia A usually bleed excessively only after trauma or surgery, those with severe hemophilia experience frequent episodes of spontaneous or excessive bleeding after minor trauma, particularly into joints and muscles. The modern management of hemophilia began in the 1970s and is actually based upon several plasma-derived or recombinant FVIII products. In addition, the synthetic drug desmopressin can be used to prevent or treat bleeding episodes in patients with mild hemophilia A. Long-term and continuous substitution therapy (prophylaxis), the recommended treatment in severe hemophilia, prevents bleeding and the resultant joint damage. In the last twenty years the high standard of hemophilia care has greatly improved the quality of life of patients and their life expectancy has reached that of the non-hemophilic male population, at least in high-income countries. The most serious and challenging complication of treatment of hemophilia A is the development of inhibitors, which renders FVIII concentrate infusion ineffective and exposes patients to an increased risk of morbidity and mortality.
• 

  Topic 12

  Programmed cell death The classification of cell death can be based on morphological or biochemical criteria or on the circumstances of its occurrence. Currently, irreversible structural alteration provides the only unequivocal evidence of death; biochemical indicators of cell death that are universally applicable have to be precisely defined and studies of cell function or of reproductive capacity do not necessarily differentiate between death and dormant states from which recovery may be possible. It has also proved feasible to categorize most if not all dying cells into one or the other of two discrete and distinctive patterns of morphological change, which have, generally, been found to occur under disparate but individually characteristic circumstances. One of these patterns is the swelling proceeding to rupture of plasma and organelle membranes and dissolution of organized structure—termed “coagulative necrosis.” It results from injury by agents, such as toxins and ischemia, affects cells in groups rather than singly, and evokes exudative inflammation when it develops in vivo. The other morphological pattern is characterized by condensation of the cell with maintenance of organelle integrity and the formation of surface protuberances that separate as membrane-bounded globules; in tissues, these are phagocytosed and digested by resident cells, there being no associated inflammation.
• 

  Topic 13

  WOUND REPAIR - Wound healing remains a challenging clinical problem and correct, efficient wound management is essential. Much effort has been focused on wound care with an emphasis on new therapeutic approaches and the development of technologies for acute and chronic wound management. Wound healing involves multiple cell populations, the extracellular matrix and the action of soluble mediators such as growth factors and cytokines. Although the process of healing is continuous, it may be arbitrarily divided into four phases: (i) coagulation and haemostasis; (ii) inflammation; (iii) proliferation; and (iv) wound remodelling with scar tissue formation. The correct approach to wound management may effectively influence the clinical outcome.
• 

  Topic 14

  Journal Club. Select a paper and present it
• 

  Topic 15

  Extracellular matrix and cancer