... last final exam at 10:00 am on May 16, I wasted no time boarding my flight to England later that afternoon. Having spent three years living in a small village near the English city of Bristol while I growing up, I had a rough idea of the cultural differences that lie in store for me when I reached Cambridge-my home for the summer.

For the first six weeks, I lived in a dorm room at Fitzwilliam College. At Cambridge, the University is only responsible for a student's academic needs. Everything else-eating, sleeping and social networking-is function of the individual colleges (there are thirty-one in all). Fitzwilliam College-or Fitz, for short-is a relatively new college, having only been established in the 1960's and takes pride in the high percentage of public-school educated students that it accepts every year. The university as a whole enrolls a large number of privately educated students in comparison to public school educated students-which over the years have reinforced the economic disparity between the students and faculty associated with the university and the citizens of Cambridge.

One of the things I most enjoyed about Cambridge was being able to walk everywhere. Even though Fitz was about a mile-and-a-half north of the city center, when the weather permitted, I made the half-an-hour journey to the lab everyday by foot. Passing over the river Cam and into the town center past centuries old houses crowding the narrow streets dotted with the infamous and historical colleges of Cambridge-Kings, Saint John's and Corpus Christi to name a few-I truly felt that I had the best commute to work that anyone could ask for. On my way home from work, I would buy locally baked organic bread, fruit and vegetables from the open air market held everyday of the week.  Occasionally, at the beginning of the summer when the undergraduates were still around, I would make a stop at King's College to attend the daily world-renowned evensong services held daily.

I was the fourth UA student to spend a summer working under Prof. Kevin Brindle in the University of Cambridge's Biochemistry Department. Prof. Brindle's research focuses mainly upon the development of new cancer imaging techniques. Prior to my arrival, I expected to work on a follow up project of an earlier study performed in the lab focusing on detecting tumor response to treatment by measuring the lactate/pyruvate ratio as detected by 13C Magnetic Resonance Imaging in tumors following injection of hyperpolarized 13C-lactate. However, due to changing priorities in the lab, I ended up investigating the molecular basis for an imaging technique currently being developed that is hypothesized to image hypoxia.

Studies performed in Malmo, Sweden by the research company Imagnia (whose focus is the investigation of new hyperolarizable compounds to be used in 13C MRI metabolic imaging) prior to my arrival in Cambridge, suggested that following an injection of hyperpolarized 13C-fumarate, the 13C-malate pool was significantly increased in tumor tissue compared to underlying skeletal muscle. Upon seeing this data, Prof. Brindle hypothesized that the phenomena was due to the fact that the tumor tissue is inherently hypoxic. Under hypoxic conditions, the transcription factor HIF-1a (Hypoxia Inducible Factor-1a) is upregulated. One of the consequences of HIF-1a activation is increased expression of pyruvate dehydrogenase kinase (PDK), and consequently pyruvate dehydrogenase phosphorylation. When PDH is phosphorylated, the pool of available acetyl-CoA available to feed into the Krebs cycle is diminished, consequently slowing flux through the entire chain of reactions. Therefore, it was hypothesized that when the 13C-fumarate was injected into the tumor tissue it was converted to malate (as the equilibrium constant of fumarase, the enzyme responsible for the conversion of fumarate to malate, favors malate formation approximately four to one). However, due to the slowing flux through the Krebs cycle, further production of oxaloacetate from the labeled malate was not possible- explaining the observation of an increase in the pool of labeled malate in tumor tissue compared to underlying skeletal muscle.

The task I was given was to test, on a molecular level, the validity of this hypothesis by developing and optimizing enzyme activity assays for PDH and fumarase. Luckily, there were known assays for each of these enzymes off of which I was able to base my work-however, as these experiments had not been performed in the Brindle lab before optimizing the conditions of these assays proved to be trickier than expected. By the end of my stay I had optimized the fumarase assay and obtained data on fumarase activity under a variety of conditions both in tumors grown in vivo and in vitro. The PDH assay proved to be much trickier, and following about a month long attempt to optimize a radiometric assay I turned my focus to optimizing a known spectrophotometric assay of PDH-due to some unexpected bumps in the road, I was not, however, able to obtain PDH activity data from tumors either in vivo or in vitro prior to my departure.

Overall, my experience in the Brindle lab was exceptional, the other students and post-docs in the lab were all friendly and more than willing to help me adjust to life in Cambridge- both inside and outside of the lab. Also during my stay, a study by the PhD student I was assigned to work with, Ferdia Gallagher, on pH imaging using hyperpolarized bicarbonate, made the cover of Nature-proof that I really was being exposed to a world-class research environment.

Sarah Nelson, UBRPer in Dr. Heddwen Brooks's lab, Physiology

Sarah's experience was funded by the MHIRT grant to UA: MD001427