Research Ideas and Methodologies

1. Identify any specific disease state for the 100,000 genes


* Targets

a. valid therapeutic target molecule

b. related molecules which may cross-react

c. transporters & metabolizing enzymes which may interact with target molecule

d. genetic variation in patient population that would impact therapeutic efficacy or toxicity

* Methodology

a. identify & characterize targets - find a small molecule which interacts with target

b. sequence genes/proteins related to target - isozymes, isoforms

c. find & sequence other genes in the pathway or pharmacologically-related - ADME - related genes (adsorption, distribution, metabolism, & excretion)

d. find genes / alleles that contribute to susceptibility, rate of progression / severity in individual patients


2. Expression profiling


* Target - cDNA or oligonucleotide arrays in various states of:

a. diseases (see if missing or too much of one mRNA)

b. tissues (e.g. specific for heart or brain?)

c. tumor (gene gone bad or making too much?)

* Methodology

a. select candidate gene that is involved in process

b. identify different alleleic forms in a population

c. genotype individuals with disease to see most common allele

d. assess if:

i. diagnostic marker (easy test to spot disease)

ii. potential drug target (find another molecule or medicine that can fix problem)


e. screening / monitoring or prophylactic intervention


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