Manuscript 1

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Combined- Chemistry & Biology

1. If you miniaturize a substance what will happen?

(a) Surface/Volume ratio decreases

(b) Surface/Volume ratio increases

(c) Mass/Volume ratio increases

(d) Mass/Volume ratio decreases

2. Mention two possible applications of Nanomaterials in Biology.

[1]

[1]

3. Optical properties of a particular metal nanomaterials depends on

(a) Size and volume

(b) Size and density

[1]

(c) mass and wieght

(d) size and shape

4. What are quantum dots? [2]

5. What is pathway engineering? Which metabolic pathway in E. coli has successfully been engineered to produce the precursor compound of the plant anti-malarial drug artemisinin? Name a few genetic factors, which are critical in reconstituting metabolic pathways to synthesize a desired herbal drug in E. coli /yeast genetic background. [2+1+2=5]

6. In an experiment on gene expression, the protein amount often fluctuates around a mean level. Explain the origin of fluctuations. [2]

7. Some microbial populations with identical genetic makeup exhibit phenotypic heterogeneity in terms of two distinct subpopulations. The subpopulations are characterized by distinct levels of expression for the same gene. Suggest a possible mechanism for the generation of this type of heterogeneity. [2]

8. What is persistence ? [2]

9. Questions (True/Flase) 8 x 1 /

2

= 4

1.

Allocombination means cells derived from same individual.

2.

Allogenic stimulation is a weak stimulation.

3.

Syngenic stimulation produces cytokines.

4.

Hybrid cells prepared from two cell types.

5.

For hybrid cell vaccination there is a need for allostimulation.

6.

T-cells play an important role in allostimulation.

7. In electrical-induced cell fusion, inhomogeneity in electric

field plays crucial role in cell fusion.

8. Short-duration electrical pulse is used for cell fusion.

10. You, being a reviewer of the journal ‘Our Journal of Chemical Biology’, have received the following manuscripts for publication in OJCB. The abstracts of the manuscripts are given below. Basing your judgements on these abstracts, give your comments (approximately 100 words) regarding the acceptability of the manuscripts in

OJCB. If one or both of them are not suitable for OJCB, you can also suggest other journals such as Biochemistry and the Journal of Molecular Biology for their publication.

[5]

Manuscript 1

Title: The I260Q Variant of DNA Polymerase β Extends Mispaired

Primer Termini Due to Its Increased Affinity for Deoxynucleotide

Triphosphate Substrates

Abstract: DNA polymerase β plays a key role in base excision repair. We have previously shown that the hydrophobic hinge region of polymerase β, which is distant from its active site, plays a critical role in the fidelity of DNA synthesis by this enzyme.

The I260Q hinge variant of polymerase β misincorporates nucleotides with a significantly higher catalytic efficiency than the wild-type enzyme. In the study described here, we show that I260Q extends mispaired primer termini. The kinetic basis for extension of mispairs is defective discrimination by I260Q at the level of ground-state binding of the dNTP substrate. Our results suggest that the hydrophobic hinge region influences the geometry of the dNTP binding pocket exclusively. Because the DNA forms part of the binding pocket, our data are also consistent with the interpretation that the mispaired primer terminus affects the geometry of the dNTP binding pocket such that the I260Q variant has a higher affinity for the incoming dNTP than wild-type polymerase β.

Manuscript 2

Title: An integrated platform of genomic assays reveals small-molecule bioactivities

Abstract:

Bioactive compounds are widely used to modulate protein function and can serve as important leads for drug development. Identifying the in vivo targets of these compounds remains a challenge. Using yeast, we integrated three genome-wide gene-dosage assays to measure the effect of small molecules in vivo . A single TAG microarray was used to resolve the fitness of strains derived from pools of (i) homozygous deletion mutants, (ii) heterozygous deletion mutants and (iii) genomic library transformants. We demonstrated, with eight diverse reference compounds, that integration of these three chemogenomic profiles improves the sensitivity and specificity of small-molecule target identification.

We further dissected the mechanism of action of two protein phosphatase inhibitors and in the process developed a framework for the rational design of multidrug combinations to sensitize cells with specific genotypes more effectively. Finally, we applied this platform to 188 novel synthetic chemical compounds and identified both potential targets and structure-activity relationships.

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