BIOL3621-WE01 BIOLOGY OF DISEASE

Answer TWO questions, each on a separate exam answer document template.

1) Explain how cytokines can be both beneficial and detrimental in the immune response to SarsCov2.

2) Discuss the functions and disease associations of small-molecule, metal-containing cofactors.

3) Table 1 below shows how tightly three human proteins (P1, P2 and P3) bind the divalent forms of magnesium, manganese, iron, cobalt, nickel and zinc plus the monovalent form of copper. Table 1 also shows the intracellular buffered availabilities of the same ionic forms of each of these metals inside the compartment of the human cell where these three proteins are made.

What does the trend in metal availabilities reveal about this compartment and why is this important for correct protein metalation? What is the predominant metal that each of these proteins bind inside this cellular compartment?

Assume that there are no metallochaperones for any of these three proteins, that the metals are not kinetically trapped by any of these proteins and hence that occupancies closely follow predictions derived at thermodynamic equilibrium. Show and explain the workings that lead you to your conclusions.

4) Until recently, RNA vaccines were impractical because of the inherent instability of mRNA and the tendency of mRNA to induce non-specific inflammatory responses. Review the experimental approaches that solved these technical problems.

5) Describe the mechanisms by which the following four proteins are known, or are likely, to contribute towards immunity:

(1) homeostatic iron regulator protein (HFE);

(2) Endoplasmic Reticulum aminopeptidase 1 (ERAP1);

(3) natural resistance-associated macrophage protein 1 (NRAMP1);

(4) calprotectin.