(3cc) Synthetic Recording of Cell Lineage and Molecular History with Image Based Readout

Embryonic development is a dynamic process in which growth and differentiation of cells are exquisitely coordinated in time and space. While there are several powerful and generalizable solutions for characterizing biological systems at a single time point, our understanding of dynamic biological processes has been severely hampered by limitations in the existing methods. Converting dynamic information to changes in the genome that can be read out by endpoint measurements offers a transformative solution. To help realize this vision, I propose to establish a platform of technologies for recording history of cells in their genome and recovering it from individual cells along with information about their spatial context and transcriptional state. This approach will allow me to address otherwise intractable questions about how distinct cell types are made during development and how deviations in this process results in disease.

Mammalian retina provides an ideal model system for this work. It is composed of more than 60 cell types wired together in a highly organized manner to enable processing of visual information. Decades of study have revealed many aspects of retinal development such as broad developmental potential of retinal progenitors, heterogeneity in clonal composition, and temporal ordering in the birth of neurons and glia. Nevertheless, it remains unclear how the regular structure of retina is built by clones with mostly random composition, to what extent retinal progenitors are biased in their fate, and how the order of neurogenesis in retina is regulated at the molecular level. To address these problems, I will develop a generalizable system that can comprehensively map the clonal composition, lineage structure, and molecular transitions in the retina, but at the same time preserve information about spatial organization of cells in the tissue. Together, these will provide fundamental new insight into cell fate specification process in mammalian retina and aid the future efforts in regenerative medicine to remedy conditions in which misspecification or degeneration of retinal neurons lead to blindness.

Successful Proposals

K99/R00 Pathway to Independence Award, NIH/NEI; 2020-2025

HHMI/Jane Coffin Childs Postdoctoral Fellowship; 2017-2020

T32 NIH Predoctoral Fellowship in Hearing and Communication Neuroscience; 2013-2015

T32 NIH NRSA Predoctoral Fellowship in Developmental Biology; 2011-2013

Postdoctoral Project

“Imaging based readout of DNA barcodes with single base pair resolution”

Under supervision of Dr. Michael Elowitz, Division of Biology and Biological Engineering, California Institute of Technology

PhD Dissertation

“Development and evolution of skeletal joints: lessons learned from studying zebrafish”

Under supervision of Dr. Gage Crump, Department of Stem Cell Biology and Regenerative Medicine, University of Southern California

Research Prior to PhD Thesis

“Computational modeling of RAG catalyzed DNA cleavage reaction”

Under supervision of Dr. Michael Lieber, Keck School of Medicine, University of Southern California

“Prokaryotic promoter prediction using an artificial neural network fed by nearest neighbors”

Under supervision of Ali Masoudi-Nejad, Institute of Biophysics and Biochemistry, University of Tehran

Selected Peer-Reviewed Publications

Askary, A., Sanchez-Guardado, L., Linton, J.M., Chadly, D.M., Budde, M.W., Cai, L., Lois, C. and Elowitz, M.B., 2020. In situ readout of DNA barcodes and single base edits facilitated by in vitro transcription. Nature biotechnology, 38(1), pp.66-75.

Askary, A., Smeeton, J., Paul, S., Schindler, S., Braasch, I., Ellis, N.A., Postlethwait, J., Miller, C.T. and Crump, J.G., 2016. Ancient origin of lubricated joints in bony vertebrates. Elife, 5, p.e16415.

Askary, A., Mork, L., Paul, S., He, X., Izuhara, A.K., Gopalakrishnan, S., Ichida, J.K., McMahon, A.P., Dabizljevic, S., Dale, R. and Mariani, F.V., 2015. Iroquois proteins promote skeletal joint formation by maintaining chondrocytes in an immature state. Developmental cell, 35(3), pp.358-365.

Askary, A., Xu, P., Barske, L., Bay, M., Bump, P., Balczerski, B., Bonaguidi, M.A. and Crump, J.G., 2017. Genome-wide analysis of facial skeletal regionalization in zebrafish. Development, 144(16), pp.2994-3005.

Askary, A., Shimazaki, N., Bayat, N. and Lieber, M.R., 2014. Modeling of the RAG reaction mechanism. Cell reports, 7(2), pp.307-315.

Askary, A., Masoudi-Nejad, A., Sharafi, R., Mizbani, A., Parizi, S.N. and Purmasjedi, M., 2009. N4: a precise and highly sensitive promoter predictor using neural network fed by nearest neighbors. Genes & genetic systems, 84(6), pp.425-430.

Teaching Philosophy

The greatest changes in my career have come through my teachers. My fourth grade teacher was instrumental in shaping my dream of becoming a scientist. In college, a course on genetic engineering taught me to see biological systems as information processing systems that can be engineered. This is still the basis of my current research. At the heart of both of these experiences is the essence of good teaching: passion for the subject matter and engaging students/mentees. Each step in my career has taught me new ways to share my passion and engage students. In addition, my interdisciplinary training taught me the importance of using real research data, which prompts integration of concepts across multiple fields. I am very excited to take this learning to a new level during my faculty appointment, both as a teacher and as a mentor.

Teaching and Mentoring Experience

Teaching was my very first job. Starting from the first year in college, I taught Physics to high school students preparing for the National University Entrance Exam in Iran. I owe a lot of my teaching skills to this experience. For example, I learned how to engage students in a large class or how to ask direct questions in a playful manner that makes it OK for students to be wrong. During my undergrad, I also served as a teaching assistant (TA) for the Analytical Chemistry course. Besides grading exams and homework, this job included holding office hours and teaching in the lab which allowed me to interact with the students directly. During my PhD, I had the opportunity to mentor multiple undergraduate and rotation graduate students who just started working in the lab. In my postdoc, so far, I have mentored two graduate students, one technician, and two international undergraduate students through Caltech’s Summer Undergraduate Research Fellowship (SURF) program.

Teaching Interests

I have a diverse training background that includes biotechnology, bioprocess engineering, developmental biology, and synthetic biology. Based on this, I am comfortable to teach a variety of courses at the intersection of biology and engineering. I am especially interested in developing new curriculums on biological circuit design, synthetic and systems biology, and microscopy and imaging. Finally, I would like to build an intense bootcamp in Biological Engineering, using small research projects that would allow new graduate students, postdocs, and interested faculty to get a taste of research at the interface between biology and engineering.