Week 1

Early in the week I met with my two advisors Dr. Harjot Singh and Dr. Laura Kirkman.  Dr. Singh is an infectious disease (ID) specialist with expertise in management of HIV/AIDS and is involved in teaching and training of medical students and ID fellows.  Dr. Kirkman is also an infectious disease specialist and runs a lab that studies the malaria parasite Plasmodium falciparum.  By working alongside both clinicians, I will be able to accumulate both clinical and research experience this summer.

On the clinical side, my time will be spent shadowing Dr. Singh and her associates as well as attending ID division events including weekly fellow talks and microbiology lab plate rounds.  I will have the opportunity to observe inpatient and outpatient care for HIV/AIDS as well as pre- and post-travel care offered at the travel clinic, which serves travelers going to/coming from areas with high prevalence of tropical and other infectious diseases.  During micro lab plate rounds, the discussion revolves around interesting and unusual microbial cultures and pathology slides encountered during the week.  Patient samples are actually brought to the meeting – cultures are passed around and microscope slides are shown using a multi-viewing microscope.  This week, a couple interesting parasitic infections were presented, one of which a patient may have contracted from a swimming pool and consequently required the hospital to get in contact with the local public health department.  For the last portion of the meeting, a case study was pulled from the CDC’s DPDx website to test the knowledge of residents and doctors alike.  Based on a list of patient symptoms and images of stained slides, the group was able to correctly identify the pathogen as Wuchereria bancrofti.

I spent the majority of my time this week in Dr. Kirkman’s lab, where I am contributing to a project that seeks to elucidate the genetic basis for drug resistance in Plasmodium falciparum.  The plasmodium proteasome is responsible for regulating protein degradation and turnover, which is crucial for transitions between stages of the parasite life cycle.  Targeting the proteasome pharmacologically is especially advantageous as disruption of protein regulation can kill all stages of the parasite.  PKS21004 is a compound that belongs to a novel class of noncompetitive proteasome inhibitors and was developed by Dr. Gang Lin’s lab at Weill Cornell.  It has been shown that low concentrations of the compound can lead to the development of drug resistant parasites, the genetic basis of which (e.g., possible point mutations in the alpha/beta subunits of the 20S proteasome) is unknown.  The overall goal of the project is to compare the genomes of normal and drug-resistant strains (Dd2 and Dd2R) of Plasmodium falciparum and elucidate any characteristics specific to the drug resistant strain.  To meet this goal, I’ve started my own cultures of malaria parasites, learned how to make blood smears and estimate parasitemia using the Giemsa stain, and designed PCR primers for the beta 1, 2, 3, and 5 subunits of the proteasome using SnapGene.