Special topics in biochemistry

Each student taking the class is to research published sources on a "special topic", and report on that research in one of several formats. The work on this semester-long project will account for about one-fifth of all graded assessments.

Choose a topic of interest to you within the field of biochemistry to research. Chapters in our text, Berg, Tymoczko, and Stryer. Biochemistry (BTS): 6th edition (2007, Freeman), that we have not covered are a good starting point. I'll be providing suggestions in class as well. Next, write an abstract or a description of what you'd like to learn, along with a short reference list (Examples of abstracts from previous student special topics reports are give below). Finally, choose a format for a final presentation, written report (~8000 words), oral (20-25 min presentation in class), online resources.

Your presentation, report, and contributions to the discussions of those of the other students will be evaluated. The range of possible topics is quite enormous, and in choosing a topic the number one guide ought to be your own interest. Perhaps something that we have studied (in either this semester or last) has sparked a desire to gain a little more in-depth knowledge, or you would like to introduce the class to a topic that we have not covered. In any case, you should attempt to relate the topic to things we have covered in the course or in Biochem I. The report should be based on at least one reasonably recent review article and several reports from the current literature. A due date before spring break) will be specified for an abstract of roughly 150 - 250 words and a reference list. For those choosing to talk to the class, you must sign up for a time to give your oral presentation (more than15 miniutes of fame!) sometime during the last two weeks of class. For those opting for written format, a draft of your report will be due on April 23, 2007. We will experiment with the course web pages and Blackboard as a means of posting drafts and continuing discussion.I encourage each student to consult with me throughout the semester (ASAP if you are having trouble deciding on a topic!) so that I can provide some guidance and direction about the topic and suggest some helpful references. A final version of your report that may incorporate changes or additions based on class feedback and discussion, and will be due during finals week.

Christene Poeller - Calcineurin and Immunosuppression

Calcineurin is a phosphatase enzyme that plays a critical role in several biological responses, including activation of cell-mediated immunity. The activity of calcineurin is specific for phosphorylated serine and threonine residues, and is regulated by intracellular calcium levels. In the immune system, calcineurin functions in a signaling pathway together with its target, a transcription complex known as NF-AT. The latter is made up of cytoplasmic and nuclear components. Dephosphorylation of the cytoplasmic component of NF-AT allows its translocation into the nucleus and formation of a complex with the nuclear component drives transcription of genes encoding cytokines, such as interleukin 2 (IL-2), and others that stimulate T-cell growth and activity. The ability of calcineurin to activate T cells is disrupted by the immunosuppressive drugs cyclosporine A (CsA) and FK506. The drugs, which are natural products of fungi, act by binding the cellular targets cyclophilin and FK-506 binding protein, respectively. These drug-target complexes then bind to and inhibit the activity of calcineurin.

References

Connor Quinn

The human immunodeficiency virus (HIV) has long been known to be the cause of AIDS. HIV is a retrovirus and like other retroviruses HIV contains a single stranded RNA genome that is replicated through a double stranded intermediate. HIV targets human helper T-cells and its viral DNA is integrated into the genome of the host T-cell where the viral genes are transcribed. The HIV viron is covered by a lipid bilayer membrane, which contains two glycoproteins: gp41 is a membrane protein that is associated with gp120 on the extracellular side. In order for the HIV to gain entry to the cell the envelope protein gp120 must bind to the CD4 receptor on the surface of the T-cell. In order for the entry to happen, HIV must bind to a coreceptor on the surface of the cell. The two major coreceptors are chemokine receptors, CCRS and CXCR4. Infection of the HIV then leads to the lyses of the helper T-cell. In this paper I will explore the mechanism of HIV and look into the specific mechanism of the chemokine receptors, which is a possible means of inhibition of the HIV virus.

References

Mc Carthy, Michael. 2002. "New HIV drugs show promise in early studies." The
Lanclet. v 359: pg 767

Mellado, Mario, et al. 2001. "Chemokine signaling and functional responses: the role of
receptor dimerization and TK pathway activation." Annual Review of Immunology.
v 19: pg. 396-421

Mack, Matthias, et al. 2000. "Endocytosis and recycling of the HIV coreceptor CCR5."
Journal of Cell Biology. v 151: pg, 1281-1293.

Aleah Smith - Medicinal biochemistry of the sialic acid pathway

The sialic acid pathway in humans is one of great interest to current research. Sialic acid, better known as N-acetylneuraminic acid, plays a major role in cell growth regulation, assists in the binding of specific proteins to membrane receptors, and facilitates cell adhesion. Interestingly, a form of sialic acid common to all other mammals, is absent in human cells. It is hypothesized that this difference could perhaps explain the greater susceptibility of humans to several cancers and various pathogens when compared to the great apes. Current research has attempted to control chemical reactivity on cell surfaces through structural alterations via oligosaccharide biosynthesis in hopes of providing the opportunity for medicines to selectively target drugs and better treat illness. The sialic acid pathway illustrates the potential of biochemical research to coalesce with medicine to offer solutions to taxing health issues.

References

1. Angata T; Varki NM; Varki A. "A second uniquely human mutation affecting sialic acid biology" J Biol Chem (26 Oct 2001) 276(43): 40282-7. [Abstract]
2. Aubin Y and Prestegard JH. "Structure and Dynamics of Sialic Acid at the Surface of a Magnetically Oriented Membrane System" Biochemistry (6 April 1993) 32(13): 3422-28. [Abstract]
   
3. Chiaramonte M; Koviach JL; Moore C, et al. "Inhibition of CMP-Sialic Acid Transport into Golgi Vesicles by Nucleoside Monophosphates" Biochemistry (27 Nov 2001) 40(47): 14260-67. [Abstract]
4. Gibbons, Ann. "Which of Our Genes Make Us Human?" Science (4 Sept 1998) 281: 1432-34.
   
5. Jacobs CL; Goon S; Yarema KJ, et al. "Substrate specificity of the sialic acid biosynthetic pathway" Biochemistry (30 Oct. 2001) 40(43): 12864-74. [Abstract]
6. Jones DH; Barber KR; Grant WM. "Minor Influence of Sialic Acid on Conformation of a Membrane-Bound Oligosaccharide Recognition Site" Biochemistry (16 April 1996) 35(15): 4803-11. [Abstract]
   
7. Mahal LK; Yarema KJ; Bertozzi CR. "Engineering Chemical Reactivity on Cell Surfaces Through Oligosaccharide Biosynthesis" Science (16 May 1997) 276: 1125-28. [Abstract]