From the Lab to the Limelight - Blog version of our #TraineeTuesday Twitter series
This #TraineeTuesday, welcome Nisha Mohd Rafiq, PhD, a former De Camilli Lab postdoc turned research group leader at University of Tübingen! Her new lab is part of the Interfaculty Institute for Biochemistry and Tübingen Neuro Campus (the university’s broader neuroscience network).
Nisha’s goal as a PI is to combine our understanding of genetic and non-genetic drivers of late-onset forms of Alzheimer’s Disease (AD) and Parkinson’s Disease (PD). She noticed that many neurodegenerative diseases share two “perplexing” aspects: 1) They are rarely genetic and 2) They often involve the aggregation of the same proteins.
Yet, almost everyone, including herself in her postdoc lab, studies the genetic forms of the disease, which account for less than 10 percent of cases. For example, a mutation in one of the proteins she studies, synaptojanin-1, only occurs in six known PD patients spanning three families. Why then do we study the rare forms? “Because frankly it is easier,” Nisha said. You can mutate a gene and study the cause-effect relationship.
However, she now has data pointing to a source of non-genetic influence.
“We now have data showing that you can cause a notorious protein to ‘aggregate’ by physically applying damage to a cytoskeleton structure called microtubules. This is not a genetic perturbation at all,” she said.
I like to think that the development of late-onset forms of AD and PD has similarity to the concept of ‘wear and tear.’ If you don’t maintain the housekeeping of some proteins, they tend to aggregate with time due to their intrinsically disordered nature.
Nisha Mohd Rafiq, PhD
Nisha does not see her lab’s launch as an accomplishment; rather, she preferred to describe it as a “platform” for her to incorporate a mechanobiological perspective when tackling neurodegenerative diseases.
She found that, by taking the chance to cross fields, she was able to create a field of her own.
Before coming to Yale, Nisha had never worked on Alzheimer’s or Parkinson’s research. She came from a vastly different PhD training. At the Mechanobiology Institute of Singapore and King’s College London in the UK, she pursued a joint PhD studying the cytoskeleton and cell mechanics. “Where no one speaks about neurons or even membrane biology!” she quipped.
Though she could have stayed in the field of mechanobiology — with many postdoc opportunities in Europe — she had always wanted to fuse membrane biology and mechanobiology. That led her to pursue a postdoc in Yale’s De Camilli Lab, which studies membrane biology.
Her interest in neuroscience was then “completely unexpected, and purely by chance,” she added. When Nisha stained a few cytoskeleton markers in neurons for an experiment, she realized exactly what she wanted to study. “I knew my own lab will merge mechanobiology in the study of neurodegeneration,” she said. Membrane biology suddenly appeared less interesting.
Her new lab’s focus reflects the most important thing she learned at Yale: the importance of asking a question from the perspective of a disease.
“I used to not care about any diseases, as I just love the architecture of the cytoskeleton in a cell because of its beauty,” Nisha said. “Now it is totally different. I always put the disease in context when asking a research question.” She left her postdoc with published work on Alzheimer’s, a preprint in revision on Parkinson’s, and another paper pending submission.
But the value of her time at Yale went beyond the research. Nisha’s favorite memory was when she accidentally formed a “small team” of select lab members in the De Camilli Lab, with whom she exchanged ideas and discussed experiments. This group proved pivotal to her projects.
As she sets up her new lab, she hopes to create a similar “chain reaction” of passion.
“I think it is important to create a team that believes in one another and genuinely wants each other to succeed as well” she said. “We often worry too much about idea ownership, prestige of a fellowship and authorship, which in my view, is so narrow-minded and meaningless in the long-term.”
Nisha also praised her previous mentors for teaching her the true definition of hard work and dedication to science. Their support brought her to where she is today, learning German and setting up her new induced pluripotent human stem cells (iPSCs) system.
“My advice to myself and to existing PIs: Don’t be a lousy mentor.”