MBG Graduate Program Entrance Exam


New students are admitted to the Graduate Program in Molecular Biology and Genetics (MBG) at the M.Sc. and Ph.D. level twice each year with students come from a variety of educational backgrounds and institutions. M.Sc. and Ph.D. students in our program form a cohesive and interactive group learning as much from each other as from the Faculty or Principal Investigator. Typically, upon completion of their education, MBG graduates go on to excellent positions in research laboratories and academic institutions worldwide, or look for additional training to complement their expertise.

Admission to MBG Graduate Programs is highly competitive and the number of applications typically exceeds the number of open positions that can be offered to Graduate Students by three-fold. General rules for the campus-wide admission requirements for the M.S. and Ph.D. programs can be found from the Boğaziçi University web page. Applicants are selected based on their performance in a written exam of Biology and an interview by MBG Faculty. On occasion, students from nontraditional backgrounds (e.g. students with undergraduate majors in Engineering or Physics) may be admitted to the program. In these cases, selection may be based less on their performance during the written exam but more on an their demonstration of aptitude in their previous discipline and enthusiasm in Biology. The Admissions Committee may stipulate (prescribe) undergraduate coursework or other means of remedial study to make up for their deficiencies in background. However, successful completion of course work with a GPA of 3.0 or greater is required to remain in the program.

The MBG Graduate Entrance Exam covers three larger areas of Molecular Biology and Genetics, based on the undergraduate material that is taught at MBG and includes: Cell Biology, Genetics, and Molecular Biology and Biochemistry. Each applicant will be presented with three questions from each field and will have to answer all (Ph.D.) or a subset (M.Sc.) of questions.

To provide you with some guidance on the type, level, and depth of Exam Questions, representative examples from previous years are listed below.


Cell Biology


  • Membrane structure and fluidity
    1. Describe the fluid mosaic model of biological membranes, indicating why such a name is appropriate for the model.
    2. Explain the factors that affect membrane fluidity. Compare/contrast the composition of membranes in a polar bear versus a desert snake.
    3. Explain why membrane fluidity is essential for the survival of biological systems.


  • Receptor Tyrosine Kinases
    The XYZ protein, which is a receptor tyrosine kinase is required for proper differentiation of a particular cell type, called MBG101. As you may know, all tyrosine kinase receptors are inactive as monomers. Binding of ligand causes the receptor to dimerize, which is followed by phosphorylation of the intracellular domain and the activation of downstream proteins. During this process, extracellular domains form disulfide bridges between two cysteines tethering the receptor tyrosine kinases.
    1. How would receptor activity be affected by changing one of the two cysteines to an alanine? Explain.
    2. Which effect would this mutation have on the differentiation of MBG101?
    3. Name three amino acids that would be likely to be found in the TM domain. What property do those amino acids have in common, and why do they cause the TM domain to stay in the membrane?
    4. Activation of the receptor tyrosine kinase causes the downstream target Ras to exchange GDP for GTP, thereby activating it. Activated Ras can initiate a signal transduction cascade, which ultimately results in the transcription of genes required for MBG101 differentiation. In a different cell type of the same organism, Ras can be activated by signaling through a growth factor receptor, which results in transcription of genes required for cell division. How can activation of the same Ras factor lead to transcription of different sets of genes in different cell types?


  • Endomembrane System
    The endomembrane system is a group of membranes and organelles in eukaryotic cells that works together to modify macromolecules.
    1. List the major components of the endomembrane system, and describe the structure and functions of each component.
    2. In your opinion, is the nuclear membrane part of the endomembrane system? Why or why not? Defend your answer.
    3. Your friend proposes that mitochondria, chloroplast and peroxisomes should be classified in the endomembrane system. Would you support or reject this proposal, explain.


  • Stem Cells
    1. Please, define embryonic stem cells (ES), adult stem cells (AS), and induced pluripotent stem cells (iPSC).
    2. Please, compare and contrast these three different stem cell varieties with regard to their potential for utilization in therapy for different kinds of diseases as well as any technical challenges.
    3. Discuss the positive and negative aspects of the use of each sub type considering ethical issues that may arise.


  • Nerve Cell Biology
    1. How is an electrical signal propagated along the axon of a nerve cells and how is the signal transmitted between cells?
    2. Which ions dominate ...
      • ...in the generation of the resting membrane potential
      • ... during depolarization
      • ... during repolarization
      • ... upon hyperpolarization.


  • Hormones
    In the human body some hormones are secreted in nanomolar quantities but are able to exert their effects on distant cells. By what kind of mechanism(s) can cells amplify a signal reaching a particular receptor?

  • Nobel Winning Reserach
    Yoshinori Ohsuma received the year 2016 Nobel Prize in Physiology or Medicine for his pioneering work on the process of autophagy in yeast.
    1. Please, define authophagy in molecular terms. What kind of conditions initiate autophagy and what would be the outcome for the cell if autophagy were to continue for an extended period of time?
    2. Please, propose an explanation for the observation that authophagy may prevent the killing of tumor cells during chemotherapy.
    3. If you were to provide a solution for this problem, what would be your approach?


Genetics


  • Genetic Inheritance
    Mendel is the father of classical genetics. Later other geneticists discovered that not all inheritance models obey Mendel’s principles.
    1. Explain the two principles of inheritance according to Mendel.
    2. You are given a pedigree of a dominantly inherited hand malformation trait. You notice that in family the trait skips a generation. How could this phenomenon be explained?
    3. A large family afflicted with Huntington disease was investigated by linkage analysis. Two children of an affected father have inherited the paternal chromosome previously identified to harbor the disease trait, yet, one of them is not affected. How could this phenomenon be explained?


  • Genome Stability
    Give a concise classification of states resulting from numerical changes in chromosome number. Explain mechanisms that can lead to polyploidy. Give examples in plants and animals. Compare the occurrence of polyploidy between these two phylogenetic groups. Name the basis of this difference.

  • Gene structure
    1. Outline the structure of a typical eukaryotic gene, including regulatory sites and other sites that are critical during transcription and translation.
    2. Indicate positions in the gene structure at which point mutations would most likely affect gene function. Explain your answers.
    3. Indicate positions in the gene structure at which point mutations would most likely not affect gene function. Explain your answers.
    4. How could the same gene serve different functions in different tissues?


  • Gene Mutation
    You are studying a grave human disease called β-thalassemia in which no β-globin protein is produced. You find that the β-globin gene’s coding region in people with this disease is normal, but that the mRNA is over a hundred nucleotides longer than normal. You sequence the β-globin gene in these people and find a single base change within the first intron of the gene. Present a hypothesis to explain the absence of β-globin in patients.

  • Mutations and Inheritance
    Suppose that you have isolated a mutant Drosophila variant that has very short wings. By chance a friend of yours, who works in a different laboratory, has also isolated a mutant flies with the same phenotype. The short wing phenotype shows a recessive inheritance pattern.
    1. How can you test if these flies have the mutation in the same gene? Please explain the test and comment on the possible results.
    2. Suppose that the observed phenotype stems from a loss-of-function mutation in the SW protein. Distinguish between a loss-of-function mutation and a gain-of-function mutation.


  • Transposable Elements
    About 45% of the human genome consists of transposons or transposable elements, but only a small percentage of those are actively moving.
    1. How can transposable elements be classified? Give a short overview of the different classes including their mode of transposition.
    2. How can transposons contribute to genetic variability?
    3. How can transposons contribute to genome evolution?


  • Transcription / Translation
    The first 21 nucleotides in the amino acid coding region of the human Huntingtin gene are 3’-TACCCACCGTTATAAGAGAGT-5’
    1. What is the sequence of the partner strand?
    2. If the DNA duplex of the gene were transcribed from left to right, deduce the base sequence of the RNA in this coding region.
    3. What would be the amino acid sequence in this part of the Huntingtin gene? (Please, use the genetic code chart given on the last page.).
    4. Suppose that a mutation in the gene occurs in the DNA sequence that replaces the red G (shown in bold) with a T. What is the nucleotide sequence of this region of the DNA duplex (both strands), and that of the messenger RNA, and what is amino acid sequence of the mutant Huntingtin protein? What is the effect of this mutation on the protein?


Molecular Biology and Biochemistry


  • Energetic Pathways
    1. Explain how a metabolic pathway can contain an energetically unfavorable reaction but still occur. Elaborate your answer in thermodynamic terms and provide one real-life example.
    2. Even though thermodynamically favorable, a reaction may still not occur spontaneously. Explain why and discuss how biological systems overcome this obstacle.
    3. Protein folding is a thermodynamically favorable event and occurs spontaneously in aqueous solutions. Why? (Hint: What are major driving forces in folding of a protein?


  • Ubiquitination
    p53 is a potent tumor suppressor often referred to as ‘the guardian of the genome’. Like thousands of other proteins in a cell, p53 (53 kDa in size) undergoes ubiquitination. This involves covalent attachment of the 8 kDa ubiquitin peptide onto p53.
    1. You have some cells in culture and would like to know what portion of total cellular p53 protein undergoes ubiquitination in these cells. You need to come up with a method to detect ubiquitinated p53. How would you do that? Explain your methodology. Any reasonably well-described technique is acceptable. Please keep in mind that you’ve got two problems:
      • ubiquitin peptide binds not only p53 but also thousands of other proteins.
      • unlike for phospho-p53 or acetly-p53, no antibody is available that recognizes ubiquitinated p53.
    2. Briefly discuss the fate of ubiquitinated proteins. What happens to them?
    3. Bortezomib (Velcade) is an FDA approved proteasome inhibitor drug developed and sold by Millenium Pharmaceuticals. It is used in the treatment of certain cancers such as multiple myeloma, though the exact mechanism of action is not known and only speculated. In your opinion, based on your answers to (a) and (b), discuss the possible reasons why Bortezomib actually works in cancer patients.


  • Analysis of Gene Expression
    You are an MD/PhD developmental biologist (highly trained in techniques of molecular biology) studying the pathogenesis of Type I insulin-dependent diabetes mellitus (IDDM). You have several patients who are predisposed to becoming diabetic, and control subjects who have no family history or predisposition to becoming diabetic, enrolled in a clinical study that will involve the removal of a small section of pancreatic beta cells. You want to analyze the differences in gene expression between cells from these two groups of subjects. Describe the experimental method(s) you would use, and what information you hope to obtain from this study.

  • Energy Metabolism
    NADH accumulates when glucose is catabolized to yield pyruvate, according to the following equation: Glucose + 2 ADP + 2 Pi + 2 NAD --> 2 Pyruvate + 2 ATP + 2 NADH. The fate of pyruvate is sometimes determined by what happens to NADH, which cannot accumulate indefinitely and is shuttled slowly into the mitochondrion, where it can be recycled.
    1. What determines whether pyruvate will be converted to lactate or oxidized to CO2 in human muscle?
    2. What determines the fate of pyruvate in yeast capable of making either vinegar or ethanol?


  • Regulation of Gene Expression
    You are interested in the newly identified iGENE signaling pathway and performed an RNA-seq experiment to identify candidate target genes that are regulated by iGENE. To do so, you overexpressed the iGENE cDNA under control of the CMV promoter in HEK293 cells and sequenced mRNA transcripts from transfected and untransfected control cells. A bioinformatic comparison revealed that 1.236 genes were upregulated, while 582 genes were downregulated when the iGENE is overexpressed. Among the upregulated genes iTARGET was expressed 16 times higher in transfected than in control cells. As a next step you now want to understand whether iTARGET is a direct target of the iGENE protein.
    1. List three different ways how you could demonstrate a direct interaction between the iGENE protein and the iTARGET gene promoter.
    2. Describe one approach in detail.
    3. How could the same iGENE protein upregulate the expression of some genes and downregulate the expression of others?


  • Genome Editing
    New tools have emerged over the recent five years to disrupt gene function, which include Zincfinger nucleases (ZFNs), Transcriptional activator linked endonucleases (TALENs) and the clustered regularly interspaced short palindromic repeats (CRISPER/Cas9) system. These complexes recognize specific DNA sequences and induce double-strand breaks at specific DNA loci.
    1. How could those tools be used for DNA editing?
    2. What are the common molecular mechanisms that are exploited here?


  • Enzyme Activity
    Name four different ways to regulate protein/enzyme activity? Briefly explain and give an example for each.

  • Hemoglobin Function
    Crocodiles have a mutated form of hemoglobin [Hb] that allows them to stay under water for up to one hour without the need to resurface to take a breath. The mutated crocodile hemoglobin [HBscuba] is sensitive to bicarbonate, which lowers its affinity to O2.
    1. What is the physiological source of bicarbonate?
    2. Human Hb is sensitive to low pH, 2,3-BPG, and CO2 similar to bicarbonate in Hbscuba, while the related oxygen carrier myoglobin is not. Explain this difference in oxygen binding of Hb and myoglobin.


  • Proteins
    Briefly explain why most globular proteins in solution:
    1. precipitate at low pH
    2. increase in solubility, then decrease in solubility, and finally precipitate as the ionic strength is increased from zero to a high value.
    3. show minimum solubility for a given ionic strength at their iso-electric pH
    4. precipitate upon heating
    5. decrease in solubility as the dielectric constant of the medium


  • Protein-Protein Interaction
    Suppose that you have identified and isolated a novel protein. Your supervisor asked you to find the interacting protein partners of this novel protein.
    1. Please name the techniques that you can use to identify the protein/s that may interact with your protein.
    2. Please explain one of these methods in detail.


  • Energy Sources
    The major energy storage compound of animals is fats (except in muscles).
    1. Why would this be advantageous?
    2. Why don’t plants use fats/oils as their major energy storage compound?
    3. Can animals convert fatty acids to glucose? How? Or Why not?


  • Recombinant Protein Expression
    Suppose that you have cloned a genomic fragment that comprises the complete sequence that codes for human insulin gene and inserted it into a prokaryotic expression vector. After you successfully transformed the expression construct into E. coli you observe that no insulin was produced by the bacteria. Propose three hypotheses to explain why you could not get insulin protein.