Interview with Dr. Salem

               On Wednesday, February 13^th 2013, our group interviewed Dr. Laura Salem (see picture below) in her office in the biology department of Rockhurst University. We selected Dr. Salem as our expert because she is a geneticist and because the main focus of our grid-computing program, dna@home, is discerning the regulation of genes through transcription factors. As all of us had been in Dr. Salem’s genetics class last semester, there was not really much need for an introduction, however, we did ask for permission to set up an interview via email beforehand. After getting the ok from Dr. Salem, we made arrangements for our interview in person.

                The questions that we had prepared for the interview revolved around several topics. We began by catching up with Dr. Salem a little bit, asking her how her holidays were, and inquiring about the signed Gary Larson cartoon she has framed in her office. Apparently, her father was once an editor for Mr. Larson. We also inquired about Dr. Salem’s education and why she became a geneticist. Dr. Salem attended Rockhurst University for her undergraduate studies before receiving her Ph. D. from Iowa University in 2000. She then did three years of post-doctorate research at UMKC studying meiotic recombination and transposable elements in yeast. For the past nine years she has been teaching at Rockhurst University. She rotates through teaching the cell biology, genetics, bio tech, general biology 1, and introduction to research courses. We then asked Dr. Salem if she was familiar with the concept of grid-computing. She responded by saying that while she is familiar with the concept, she has not participated in grid-computing herself. She mentioned some interest in the application of grid-computing and thought that genetics was a particularly apt field to which it could be applied.

                From here, our questions turned more pointedly to the nature of gene regulation. We began by simply asking how cells regulate what genes they express and how often they express them. Dr. Salem professed that she was not an expert on gene regulation; however we found that hard to believe as this simple question unlocked a wealth of information possessed by Dr. Salem. She walked us through a brief overview of the transcription process by which a cell fabricates mRNA. During this process, an enzyme called polymerase attaches to a gene which is composed of a sequence of nucleotides on the DNA. The polymerase then travels down the DNA strand and transcribes the genetic code into a complementary strand of mRNA which is then transported out of the cell that it may be used to make proteins. Small proteins called transcription factors help the larger polymerase locate and attach to the correct gene so that it may then start making mRNA. A particular kind of transcription factor, called an enhancer, is especially important in up-regulating the expression of genes. Conversely, some transcription factors known as insulators may attach to the DNA strand and serve to help keep a gene “turned off” by blocking the polymerase from attaching. See below for a diagram displaying transcription factors.

This description of transcription and the ways in which transcription factors affect it spurred us to ask this follow up question: Are there any other ways in which scientists can help manipulate a cell so that certain genes are expressed more? Dr. Salem then went on to describe how we can sometimes aid a cell in expression a gene more often through histone interactions. We asked what histones were and she told us that they are proteins that aid in the ordering and packaging of DNA molecules. They essentially act as spindles around which DNA molecules are wound into structures called nucleosomes. Dr. Salem elaborated by saying that a DNA molecule must be unwound from around its histone before transcription ban take place. This is because the two strands of DNA must be broken apart from each other so that polymerase can read the nucleotide sequence and fabricate mRNA. Because there is not enough room in between the two strands of DNA for polymerase to fit, the DNA must be uncoiled. Some scientists are taking advantage of this knowledge by forcing DNA to remain uncoiled for longer periods of time. This allows the cell to make more copies of mRNA from the gene which may in turn be used to make more proteins. A diagram of histones can be found below.

To wrap the interview up, we asked Dr. Salem if there was anything else that we had missed that we should know. She noted that we should distinguish between two types of genes. There are genes within a cell that code for proteins that are so necessary for normal function that they are, in a sense, always turned on. Other genes, however, code for proteins that may have a much more dramatic affect within a cell. Dr. Salem surmised that gene regulation therapy, if applied to medical science, will most likely focus on these genes rather than the basal “always on” type genes. Furthermore, as a piece of advice for our group as we continue to study the nature of gene regulation, Dr. Salem warned us that the field of genetics is a very vast one. Many scientists devote their entire lives to studying very specific aspects of genetics and gene regulation. She therefore suggested that we narrow the scope of any future research that we may conduct for fear of being overwhelmed. We then thanked Dr. Salem for her time and told her how much we enjoyed talking with her. She wished us the best of luck on our blog and said she would look into grid-computing a little more. The interview lasted approximately thirty-five minutes as Dr. Salem had a department meeting she needed to attend.

As a result of this interview, we learned much about the regulation of genes due to the manipulation of histones and transcription factors. This was especially pertinent information to dna@home as it is devoting processing power to search for the nucleotide sequences that transcription factors bind to in the genomes of Yersinia pestis and Mycobacterium tuberculosis. As a group, we now possess a better understanding of both the importance of finding these elusive nucleotide sequences and what can be done with them once they are found.