Dr. Jason Evans is a teacher, researcher, and analytical chemist with a penchant for the science of chemistry. “The deep-seated beauty that the subject holds -” he said, “-it’s almost like a light bulb when it goes on. It’s like, wow!”
Evans earned his post-doctoral degree doing some fascinating research at the National Institutes of Health. There he was part of a team that investigated the biosynthesis of an important energy molecule in human cells called NAD. Depending on the outcome of further tests, the research may serve as a basis for the treatment of AIDS-caused dementia.
Dementia in AIDS happens when immune cells called macrophages, which Evans called “rescue” cells, attack the AIDS virus in the brain, but leave damaging levels of toxins in their wake.
Said Evans, “It wasn’t clear exactly what was going on with it, but there was some evidence that higher levels of NAD in these cells seemed to have the effect of cleaning up the toxins left over.”
“NAD is nucleotide that’s in every cell and is an energy molecule. What happens is that NAD undergoes what’s called a reduction oxidation reaction. That simply means that electrons are being transferred between the NAD and something else in the cell. That transfer of electrons can be a way of transferring energy to the cell.”
What Evans and the team needed to do was figure out the “biosynthetic pathways for [making] NAD in cells like macrophages. If we can boost the levels of NAD in macrophages, we could maybe lessen the effects of AIDS dementia.”
Evans explained that his main contribution to the work was his expertise as an analytical chemist. (There are five main branches of chemistry: physical, analytical, organic, inorganic and biochemistry.) Evans had expertise in the instruments that would be needed to measure and identify chemical compounds from cultured cells. The research team needed to “separate complex mixtures of biological compounds” and identify them.
To do this, Evans used something called LC MS. As he explained, LC MS is actually a combination of two instruments. One is the HPLC (“high-pressure liquid chromatography”) section which separates the compound. The HPLC, Evans demonstrated holding a handy oblong box, is a small column through which an organic mixture flows. “You have an injector that can inject your sample midstream in that flow.”
“Now the inside of the column is packed with little glass beads that have coatings on them. The coatings have chemical properties – they’re really just hydrocarbons. Your components in your sample are able to interact with the coatings on the beads…The molecules you’re trying to separate will have different affinities for that coating. Since they different affinities – when they’re actually stuck to the coating – at times certain molecules not going to be moving down the column. They’ll be held in place. When the molecules are not interacting they’re going to be moving down.”
The different molecules exit the HPLC instrument at different times. When they elute, they are detected by the second instrument, the mass spectrometer, (MS). The mass spectrometer, Evans said, is a huge instrument. It “measures the molecular mass of the components coming off ” the HPLC. Each component molecule has a signature mass and structure. Evans’ job included having to research the standard mass of each molecule and match it to what was coming from the cultured sample. (A computerized database of the molecular masses of components of non-volatile compounds does not yet exist for the mass spectrometer.)
“As these molecules separate,” Evans elaborated, “and go into the mass spectrometer, we see a peak that illustrates that ‘this’ peptide has a molecular mass of ‘this’. You can take it one step further – force that complex to fall apart in characteristic ways and measure the fragments of how it falls apart. By having a spectrum of the mass of those fragments, we can put together the puzzle. Figure out the composition and structure of the peptide.”
Sounds like hard work? “It’s fun,” Evans said. In the NIH project, Evans and the others discovered that one of NAD’s precursors (materials that build a molecule), quinolinic acid, seemed to increase the production of NAD when it was added to cultured cell samples.
They had to label the quinolinic acid by increasing its molecular mass by 1, “replacing the carbon-12s with carbon-13s and replacing nitrogen-14s with nitrogen-15s”. (The numbers represent the number of protons of an element.) “There are 10 carbons in quinolinic acid so the weight of that [altered] quinolinic acid was 10 mass units higher than the normal mass. If we feed that label into the media then the NAD that gets produced from that labeled precursor will also be 10 mass units higher [than the standard molecule of NAD].”
“So now I can say how much of the NAD was made from [NAD’s] other two biosynthetic pathways and how much was made from the quinolinic acid.” While the work was exciting and necessary, it will take more research – to discover how quinolinic is stimulating production of NAD – before the data can be used for treatment of dementia.
While he continues to do research, Evans also heeds the call of the classroom. He explained that he started teaching while a graduate student. “I taught laboratory extensions as a teaching assistant. I worked for a man who was fantastic – one of the top guys in the field early on. He had got to the point where loved teaching so much the research wasn’t a big priority for him. He focused on his students. He had such a wonderful time doing it – I had such a wonderful time in lab, that I knew that’s what I wanted to do.”
Evans said he feels comfortable bringing “the research to the undergraduates.” He and his students at UMB are currently conducting experiments to measure the energy of certain chemical reactions.
Evans said it is part of his teaching mission to inspire love for the science in undergraduate chemistry majors. “The truly difficult part about doing that is that so much of science, especially chemistry, is a building block. You’re taught these building blocks and sometimes it seems like you’re climbing this mountain and you never get to see the good view. Many times, it’s not until they’re through with their undergraduate career that they can see the view. The challenge is to provide glimpses of that view along the way. It’s important to get that as an undergraduate.”
Evans said he likes the diversity of UMass Boston and “the fact that most of your students are coming back after seeing the world and therefore, are inspired to do great work. What’s a little bit different about this place – something that makes it challenging – is that the scales of abilities in one course seem to be like no place I could ever imagine. The difference between the top five students and the bottom five students is challenging to deal with. The way I try to deal with it is by having my door open all the time.” Evans said he lets students know they can have extra time with him and with tutors and that “if the lower five students want to be helped they can be helped.”
Evans backs his words with action. He recently applied for a grant to purchase an HPLC-Mass Spectrometer for UMB and his grant was funded. Sometime soon the school will receive its first such instrument.